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10.1126/science.2814477 | 38,398,556 | Two human cell lines (termed ρ 0 ), which had been completely depleted of mitochondrial DNA (mtDNA) by long-term exposure to ethidium bromide, were found to be dependent on uridine and pyruvate for growth because of the absence of a functional respiratory chain. Loss of either of these two metabolic requirements was us... | 10.1038/nrg3275 | This was the first description of the use of cybrid technology in mammalian cells. |
10.1111/j.1750-3639.1992.tb00679.x | 27,071,316 | Molecular genetics, biochemistry, immunology and morphology, are being applied in a coordinated fashion to unveil the molecular basis of the mitochondrial encephalomyopathies. Mutations of mitochondrial DNA (mtDNA) have been found in well characterized clinical groups of these disorders. New and old morphologic methods... | 10.1038/nrg3275 | In this paper, a comprehensive survey is presented of morphological approaches used to diagnose and study mitochondrial diseases. |
10.1152/ajplung.00382.2007 | 19,844,674 | Recent evidence suggests that dysfunctional type II alveolar epithelial cells (AECs) contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF). Based on the hypothesis that disease-causing mutations in surfactant protein C ( SFTPC) provide an important paradigm for studying IPF, we investigated a potential ... | 10.1038/nrd.2017.170 | This report shows that ER stress and UPR activation are found in alveolar epithelial cells in the lungs of patients with sporadic and familial IPF and may contribute to its pathogenesis. |
10.1073/pnas.0701009104 | 41,469,178 | Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung disease of unknown etiology. Some individuals with IPF have a familial disorder that segregates as a dominant trait with incomplete penetrance. Here we used linkage to map the disease gene in two families to chromosome 5. Sequencing a candidat... | 10.1038/nrd.2017.170 | References 23 and 24 demonstrate that mutations in the genes encoding telomerase components that result in telomere shortening confer an increase in susceptibility to adult-onset familial IPF. |
10.1126/scitranslmed.3008182 | 125,293,370 | Fibrosis resolution is impaired by aging and is mediated by altered cellular redox homeostasis because of a Nox4-Nrf2 imbalance that promotes an apoptosis-resistant myofibroblast phenotype. | 10.1038/nrd.2017.170 | Genetic and pharmacological targeting of NOX4 in ageing mice diminished the senescence of fibroblasts and reversed persistent fibrosis. |
10.1038/ncomms14532 | 83,294,437 | Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regula... | 10.1038/nrd.2017.170 | Studies using the bleomycin lung fibrosis model showed that deletion of p16 INK4 -positive cells or the use of the senolytic cocktail dasatinib plus quercetin improved lung function and reduced the secretion of SASP factors. |
10.1073/pnas.95.24.14060 | 100,815,874 | Previous studies of the annexin family of Ca 2+ binding proteins identified a soluble monomer in the absence of Ca 2+ and a trimer adsorbed on the membrane surface in the presence of Ca 2+ . On the basis of site-directed spin-labeling studies of annexin XII at low pH, we now report a membrane-inserted form of the prote... | 10.1038/nrm1661 | This study used a site-specific spin-labelling approach to describe a transmembrane form of the Hydra annexin B12 that is proposed to result from a conformational rearrangement induced by acidic pH values. |
10.1083/jcb.132.6.1079 | 38,595,226 | Cultures of the nematode C. elegans were examined for the presence of calcium-dependent, phospholipid-binding proteins of the annexin class. A single protein of apparent mass on SDS-polyacrylamide gels of 32 kD was isolated from soluble extracts of nematode cultures on the basis of its ability to bind to phospholipids ... | 10.1038/nrm1661 | This study describes the identification of the main C. elegans annexin, NEX-1, and its striking enrichment on the cytoplasmic surface of membranes of the spermathecal valve. |
10.1083/jcb.200311054 | 41,473,685 | Annexins are Ca2+-binding, membrane-fusogenic proteins with diverse but poorly understood functions. Here, we show that during cell cycle progression annexin 11 translocates from the nucleus to the spindle poles in metaphase and to the spindle midzone in anaphase. Annexin 11 is recruited to the midbody in late telophas... | 10.1038/nrm1661 | By employing RNA interference to downregulate annexin A11, these authors show that this annexin functions in the terminal phase of cytokinesis, possibly participating in the delivery of new membrane material that is required for abscission. |
10.1083/jcb.142.6.1413 | 59,318,316 | A member of the annexin XIII sub-family, annexin XIIIb, has been implicated in the apical exocytosis of epithelial kidney cells. Annexins are phospholipid-binding proteins that have been suggested to be involved in membrane trafficking events although their actual physiological function remains open. Unlike the other a... | 10.1038/nrm1661 | An elegant paper showing that in polarized epithelial cells the myristoylated form of annexin A13b functions in the formation and apical delivery of transport vesicles that are rich in lipid microdomains. |
10.1091/mbc.e03-06-0387 | 28,233,784 | The Ca 2+ - and lipid-binding protein annexin 2, which resides in a tight heterotetrameric complex with the S100 protein S100A10 (p11), has been implicated in the structural organization and dynamics of endosomal membranes. To elucidate the function of annexin 2 and S100A10 in endosome organization and trafficking, we ... | 10.1038/nrm1661 | References 80 and 82 used the RNA-interference-mediated depletion of annexin A2 to show that this protein is involved in early endosome dynamics — that is, in maintaining the morphological appearance of recycling endosomes and in the biogenesis of multivesicular endosomes, respectively. |
10.1073/pnas.0400441101 | 103,523,871 | Modulation of cholesterol absorption in the intestine, the primary site of dietary cholesterol uptake in humans, can have profound clinical implications. We have undertaken a reverse genetic approach by disrupting putative cholesterol processing genes in zebrafish larvae by using morpholino (MO) antisense oligonucleoti... | 10.1038/nrm1661 | Describes the involvement of an annexin-A2–caveolin-1 complex in intestinal sterol transport. |
10.1189/jlb.1103552 | 3,387,102 | Abstract This overview will focus on one aspect of neutrophil biology, which is the selective activation of the annexin 1 system in relation to the process of cell extravasation. Besides the current view about the biochemistry of annexin 1 and annexin 1 receptor(s) up-regulation within the microenvironment of the adher... | 10.1038/nrm1661 | An excellent review by two key investigators who work on the anti-inflammatory actions of annexin A1. |
10.4049/jimmunol.172.12.7669 | 59,124,201 | Abstract The human N-formyl peptide receptor (FPR) is a key modulator of chemotaxis directing granulocytes toward sites of bacterial infections. FPR is the founding member of a subfamily of G protein-coupled receptors thought to function in inflammatory processes. The other two members, FPR-like (FPRL)1 and FPRL2, have... | 10.1038/nrm1661 | References 108 and 109 show that annexin A1 also functions as an agonist of the FPR-like receptors FPRL1 and FPRL2. |
10.1073/pnas.151174198 | 39,873,957 | Normal levels of CD4 + regulatory T cells are critical for the maintenance of immunological homeostasis and the prevention of autoimmune diseases. However, we now show that the expansion of CD4 + regulatory T cells in response to a chronic viral infection can lead to immunosuppression. Mice persistently infected with F... | 10.1038/nri1029 | This study provides the first evidence of an important role for T Reg cells in controlling the immunopathology of infectious disease. |
10.1126/science.1073514 | 102,387,861 | Antigen-presenting cells (APCs) can induce tolerance or immunity. We describe a subset of human APCs that express indoleamine 2,3-dioxygenase (IDO) and inhibit T cell proliferation in vitro. IDO-positive APCs constituted a discrete subset identified by coexpression of the cell-surface markers CD123 and CCR6. In the den... | 10.1038/nri1029 | References 97 and 98 show a new mechanism by which antigen-presenting cells can induce tolerance in their local microenvironment by depleting tryptophane. CTLA4 and IFN-γ can induce the expression of IDO, which catabolizes tryptophane and mediates tolerance. |
10.2337/diacare.27.10.2356 | 81,457,920 | OBJECTIVE— Glycemic control using inhaled, dry-powder insulin plus a single injection of long-acting insulin was compared with a conventional regimen in patients with type 2 diabetes, which was previously managed with at least two daily insulin injections. RESEARCH DESIGN AND METHODS— Patients were randomized to 6 mont... | 10.1038/nrd4477 | Presents results from a clinical trial demonstrating safety and efficacy of the inhaled insulin formulation Exubera. |
10.1083/jcb.69.3.717 | 20,107,350 | In Saccharomyces cerevisiae, a highly ordered ring of 10-nm filaments is intimately associated with the plasma membrane within the neck of the bud. The ring is formed during early bud emergence and disappears when cytokinesis begins. | 10.1038/nrm2407 | This classic EM study identified the 10-nm striations at the S. cerevisiae bud neck that would become known as the septin collar. |
10.1016/j.febslet.2007.10.032 | 122,860,579 | Septins, a conserved family of cytoskeletal GTP‐binding proteins, were presented in diverse eukaryotes. Here, a comprehensive phylogenetic and evolutionary analysis for septin proteins in metazoan was carried out. First, we demonstrated that all septin proteins in metazoan could be clustered into four subgroups, and th... | 10.1038/nrm2407 | This study provides detailed phylogenetic analyses of septins in both fungi and animals. See also reference 15. |
10.1091/mbc.e04-08-0734 | 41,465,640 | Budding yeast has been a powerful model organism for studies of the roles of actin in endocytosis and septins in cell division and in signaling. However, the depth of mechanistic understanding that can be obtained from such studies has been severely hindered by a lack of ultrastructural information about how actin and ... | 10.1038/nrm2407 | This study provides the first high-resolution views of cortical septin structures in yeast cells using rapid-freeze and deep-etch EM. |
10.1126/science.1099892 | 82,393,810 | During cytokinesis, furrow ingression and plasma membrane fission irreversibly separate daughter cells. How actomyosin ring assembly and contraction, vesicle fusion, and abscission are spatially coordinated was unknown. We found that during cytokinesis septin rings, located on both sides of the actomyosin ring, acted a... | 10.1038/nrm2407 | This study shows that septin rings act as barriers to compartmentalize the cortex around the site of cytokinesis. |
10.1126/science.290.5490.341 | 18,938,737 | Asymmetric localization of proteins plays a key role in many cellular processes, including cell polarity and cell fate determination. Using DNA microarray analysis, we identified a plasma membrane protein-encoding mRNA (IST2) that is transported to the bud tip by an actomyosin-based process. mRNA localization created a... | 10.1038/nrm2407 | This study demonstrates that a membrane protein specifically translated in the bud is retained in the bud plasma membrane via a septin-dependent diffusion barrier. |
10.1073/pnas.0803330105 | 4,645,430 | Mitotic yeast cells express five septins (Cdc3, Cdc10, Cdc11, Cdc12, and Shs1/Sep7). Only Shs1 is nonessential. The four essential septins form a complex containing two copies of each, but their arrangement was not known. Single-particle analysis by EM confirmed that the heterooligomer is octameric and revealed that th... | 10.1038/nrm2407 | In this study, the architecture of the S. cerevisiae septin core complex was determined using biochemistry and EM. |
10.1126/science.166.3906.753 | 101,068,080 | Neonatal thymectomy of mice, when no ectopic thymus existed, constantly resulted in developmental arrest of the ovary but not of the testis; it also caused sterility in the female. The ovaries of thymectomized mice were extremely small and were characterized by absence of follicles and corpora lutea. Such an ovarian dy... | 10.1038/nri1026 | Day-3 thymectomy of non-autoimmune-prone BALB/c mice induces autoimmune disease (ovaritis). |
10.1084/jem.184.2.387 | 38,797,407 | Neonatal thymectomy (NTx), especially around day 3 after birth, causes various organ-specific autoimmune diseases in mice. This report shows that: (a) T cells expressing the interleukin 2 receptor alpha chains (CD25) ontogenically begin to appear in the normal periphery immediately after day 3, rapidly increasing withi... | 10.1038/nri1026 | The polyautoimmune syndrome that is induced by day-3 thymectomy can be prevented by the administration of purified CD4 + CD25 + T cells. |
10.1084/jem.177.3.627 | 83,484,091 | Diabetes was induced in a normal nonautoimmune rat strain by rendering the animals relatively T cell deficient using a protocol of adult thymectomy and sublethal gamma irradiation. All male rats and 70% of females developed an acute syndrome with severe loss of weight and hyperglycemia. Diabetes in these lymphopoenic r... | 10.1038/nri1026 | Sub-lethal irradiation of adult thymectomized rats induces diabetes and thyroiditis. The onset of these two diseases can be prevented by infusion of CD4 + RT6 + T cells. |
10.1084/jem.162.5.1683 | 79,373,169 | DA rats grafted with major histocompatibility complex-incompatible PVG heart grafts and treated with cyclosporine (CY) for 10 d do not reject their grafts, and develop a state of specific unresponsiveness toward PVG allografts. Cells from these animals tested in an adoptive transfer assay were incapable of restoring PV... | 10.1038/nri1026 | This study provides the first evidence that transplantation tolerance can be transferred to naive recipients by CD4 + CD25 + T cells. |
10.1126/science.8094901 | 104,157,879 | The maintenance of transplantation tolerance induced in adult mice after short-term treatment with nonlytic monoclonal antibodies to CD4 and CD8 was investigated. CD4 + T cells from tolerant mice disabled naïve lymphocytes so that they too could not reject the graft. The naive lymphocytes that had been so disabled also... | 10.1038/nri1026 | The first demonstration of infectious tolerance in a transplantation model. |
10.1084/jem.169.5.1669 | 67,060,171 | The nonobese diabetic (NOD) mouse has recently been introduced as a model for insulin-dependent diabetes mellitus. The role of regulatory T cells in the development of antipancreatic autoimmunity in this model remains unclear. To evaluate the presence of suppressive phenomena, we used disease transfer by spleen cells f... | 10.1038/nri1026 | The first demonstration that CD4 + T cells can prevent the onset of a spontaneous autoimmune disease, namely insulin-dependent diabetes mellitus in non-obese diabetic (NOD) mice. |
10.1084/jem.174.4.791 | 28,039,276 | Suppression of experimental autoimmune encephalomyelitis (EAE) in Lewis rats by the oral administration of myelin basic protein (MBP) is mediated by CD8+ T cells that can be isolated from the spleens of MBP-fed animals. These cells adoptively transfer protection to naive animals subsequently immunized with MBP and comp... | 10.1038/nri1026 | This study shows that tolerance induced by oral administration of myelin basic protein extends to other myelin antigens, providing the first demonstration of bystander suppression. |
10.1073/pnas.0900141106 | 59,258,655 | Epilepsy, a disease characterized by abnormal brain activity, is a disabling and potentially life-threatening condition for nearly 1% of the world population. Unfortunately, modulation of brain excitability using available antiepileptic drugs can have serious side effects, especially in the developing brain, and some p... | 10.1038/nrd2997 | This study suggests that a cell-grafting strategy could be used to treat complex neurological disorders such as epilepsy. It provides proof of concept for the use of embryonic stem cell implants to enhance inhibitory neurotransmission. |
10.1073/pnas.240458997 | 59,263,577 | Cell division and differentiation continue throughout the plant life cycle without significant loss of control. However, little is known about the mechanisms that allow the continuous development of meristems. Cell division is controlled by a family of cyclin-dependent kinases (CDKs). CDK-activating kinases (CAKs) are ... | 10.1038/nrm2227 | A comprehensive study illustrating that the level of CDK activity controls the differentiation status of root initial cells. |
10.1105/tpc.105.040485 | 871,697 | Abstract PASTICCINO2 (PAS2), a member of the protein Tyr phosphatase-like family, is conserved among all eukaryotes and is characterized by a mutated catalytic site. The cellular functions of the Tyr phosphatase-like proteins are still unknown, even if they are essential in yeast and mammals. Here, we demonstrate that ... | 10.1038/nrm2227 | Identifies the PAS2 antiphosphatase as a novel CDK regulatory protein. PAS2 interacts specifically with tyrosine-phosphorylated CDKA;1, thereby shielding this particular CDK from putative activating phosphatases. The interaction between PAS2 and CDKA;1 probably marks the onset of cell differentiation. |
10.1105/tpc.106.044834 | 19,269,159 | Abstract Recessive mutations in the SIAMESE (SIM) gene of Arabidopsis thaliana result in multicellular trichomes harboring individual nuclei with a low ploidy level, a phenotype strikingly different from that of wild-type trichomes, which are single cells with a nuclear DNA content of ∼16C to 32C. These observations su... | 10.1038/nrm2227 | Describes a novel group of CDK inhibitory proteins. One member, designated SIAMESE, has a prominent role at the mitosis-to-endocycle transition in trichome cells. |
10.1105/tpc.106.045047 | 29,171,261 | Abstract Upon the incidence of DNA stress, the ataxia telangiectasia–mutated (ATM) and Rad3-related (ATR) signaling kinases activate a transient cell cycle arrest that allows cells to repair DNA before proceeding into mitosis. Although the ATM-ATR pathway is highly conserved over species, the mechanisms by which plant ... | 10.1038/nrm2227 | Shows that the A. thaliana WEE1 gene is not rate limiting for cell-cycle progression under normal growth conditions, but instead is a critical target of the ATR/ATM signalling cascades that inhibit the cell cycle following activation of the DNA integrity checkpoints. |
10.1073/pnas.0404833101 | 104,361,526 | Siglecs are a recently discovered family of animal lectins that belong to the Ig superfamily and recognize sialic acids (Sias). CD33-related Siglecs (CD33rSiglecs) are a subgroup with as-yet-unknown functions, characterized by sequence homology, expression on innate immune cells, conserved cytosolic tyrosine-based sign... | 10.1038/nri2056 | This extensive bioinformatics analysis on rodent and primate genome sequences establishes that the CD33-related Siglecs are rapidly evolving and exhibit striking differences in repertoire between mammalian species. |
10.1182/blood.v85.8.2005.bloodjournal8582005 | 19,698,353 | CD33 is a member of the Ig superfamily that is restricted to cells of the myelomonocytic lineage but whose functions and binding properties are unknown. It shares sequence similarity with sialoadhesin, CD22, and the myelin-associated glycoprotein, which constitute the Sialoadhesin family of sialic acid-dependent cell a... | 10.1038/nri2056 | This is the first paper to show that CD33 can function as a sialic-acid binding lectin. Together with reference 38, this paper establishes that Siglecs can be masked when expressed at the cell surface and that unmasking can occur following sialidase-treatment of Siglec-expressing cells. |
10.1126/science.7618087 | 100,645,663 | CD22 is a membrane immunoglobulin (mIg)-associated protein of B cells. CD22 is tyrosine-phosphorylated when mIg is ligated. Tyrosine-phosphorylated CD22 binds and activates SHP, a protein tyrosine phosphatase known to negatively regulate signaling through mIg. Ligation of CD22 to prevent its coaggregation with mIg lowe... | 10.1038/nri2056 | This is one of the first papers to clearly demonstrate that CD22 functions as an inhibitory receptor of B cells via interactions with SHP1. It also shows that antibody-induced sequestration of CD22 away from the BCR lowers the threshold for B-cell activation by 100-fold. |
10.1182/blood-2004-10-4112 | 123,334,934 | Abstract We report about new apoptotic and non-apoptotic death pathways in neutrophils that are initiated via the surface molecule sialic acid-binding immunoglobulin-like lectin (Siglec)-9. In normal neutrophils, Siglec-9 ligation induced apoptosis. Inflammatory neutrophils obtained from patients with acute septic shoc... | 10.1038/nri2056 | This paper and reference 94 are the first to show that ligation of Siglecs on granulocytes can trigger cell-death signals that are enhanced in the presence of cytokines that normally promote cell survival. |
10.1182/blood-2006-08-039255 | 18,781,723 | Abstract CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation ... | 10.1038/nri2056 | First demonstration of an inhibitory function for a CD33-related Siglec. |
10.1128/cmr.14.3.547-560.2001 | 123,667,465 | SUMMARY Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for di... | 10.1038/nrg820 | A thorough review that details current microbial nomenclature and concepts of evolutionary and population-based genetics. It reviews various molecular techniques and makes recommendations for their application in epidemiology, taxonomy and evolutionary studies. |
10.1146/annurev.micro.55.1.561 | 18,658,728 | ▪ Abstract The population structures of bacterial species are complex and often controversial. To a large extent, this is due to uncertainty about the frequency and impact of recombination in bacteria. The existence of clones within bacterial populations, and of linkage disequilibrium between alleles at different loci,... | 10.1038/nrg820 | This review addresses the impact of recombination on bacterial populations and gives specific focus to multilocus sequence typing. |
10.1073/pnas.95.6.3140 | 62,077,419 | Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic ... | 10.1038/nrg820 | This paper introduces multilocus sequence typing as a method for typing microorganisms on the basis of the nucleotide sequences of a limited number of genetic loci. |
10.1073/pnas.97.26.14668 | 101,081,481 | Helicobacter pylori colonizes the stomach of half of the world's population, causing a wide spectrum of disease ranging from asymptomatic gastritis to ulcers to gastric cancer. Although the basis for these diverse clinical outcomes is not understood, more severe disease is associated with strains harboring a pathogenic... | 10.1038/nrg820 | This study provided the first evidence of the extent of genetic diversity in bacteria using microarray analysis. |
10.1128/aem.67.12.5780-5790.2001 | 61,206,764 | ABSTRACT To determine the potential of DNA array technology for assessing functional gene diversity and distribution, a prototype microarray was constructed with genes involved in nitrogen cycling: nitrite reductase ( nirS and nirK ) genes, ammonia mono-oxygenase ( amoA ) genes, and methane mono-oxygenase ( pmoA ) gene... | 10.1038/nrg820 | This crucial study describes conditions for examining gene composition in natural microbial communities using microarray analysis. |
10.1128/aem.67.8.3677-3682.2001 | 45,556,257 | ABSTRACT Whole genomic DNA-DNA hybridization has been a cornerstone of bacterial species determination but is not widely used because it is not easily implemented. We have developed a method based on random genome fragments and DNA microarray technology that overcomes the disadvantages of whole-genome DNA-DNA hybridiza... | 10.1038/nrg820 | A method based on random genome fragments and DNA microarray technology that reveals taxonomic relationships between bacterial strains. |
10.1128/iai.69.12.7832-7838.2001 | 18,817,294 | ABSTRACT Helicobacter pylori has a very plastic genome, reflecting its high rate of recombination and point mutation. This plasticity promotes divergence of the population by the development of subclones and presumably enhances adaptation to host niches. We have investigated the genotypic and phenotypic characteristics... | 10.1038/nrg820 | By using microarray analysis, the authors detected genetic changes between clinical isolates collected from a single patient, alluding to the potential for in vivo sub-species development. |
10.1073/pnas.251551698 | 82,885,679 | Isolates of the gastric pathogen Helicobacter pylori harvested from different individuals are highly polymorphic. Strain variation also has been observed within a single host. To more fully ascertain the extent of H. pylori genetic diversity within the ecological niche of its natural host, we harvested additional isola... | 10.1038/nrg820 | This study used microarrays to examine the extent and types of genetic change in a bacterial pathogen that occur during long-term host colonization and how these correlate with clinical outcomes of infection. |
10.1128/iai.69.4.2477-2486.2001 | 28,215,338 | ABSTRACT Streptococcus pneumoniae remains a major causative agent of serious human diseases. The worldwide increase of antibiotic resistant strains revealed the importance of horizontal gene transfer in this pathogen, a scenario that results in the modulation of the species-specific gene pool. We investigated genomic v... | 10.1038/nrg820 | These authors used an Affymetrix high-density oligonucleotide array to examine the genetic relatedness of 20 clinical S. pneumoniae isolates, 5 Streptococcus mitis isolates and 4 Streptococcus oralis isolates. |
10.1242/dev.125.10.1921 | 125,287,144 | Any epithelial portion of a normal mouse mammary gland can reproduce an entire functional gland when transplanted into an epithelium-free mammary fat pad. Mouse mammary hyperplasias and tumors are clonal dominant populations and probably represent the progeny of a single transformed cell. Our study provides evidence th... | 10.1038/nrm1714 | Provides evidence for the existence of lineage-committed cells in mammary epithelium. |
10.1073/pnas.222549599 | 106,599,157 | The cytokine hormones prolactin and erythropoietin mediate tissue-specific developmental outcomes by activating their cognate receptors, prolactin receptor (PrlR) and erythropoietin receptor (EpoR), respectively. The EpoR is essential for red blood cell formation, whereas a principal function of PrlR is in the developm... | 10.1038/nrm1714 | Shows that the intracellular domains of the EPO and PRL receptors display equivalent functions, and that the EPO- and PRL-specific responses depend on the cellular context. |
10.1101/gad.880801 | 100,831,427 | Prolactin is essential for proliferation and differentiation of the developing mammary gland. We have explored a role for Suppressor of Cytokine Signaling 1 (SOCS1) as a modulator of the prolactin response using mice deficient in SOCS1, which were rescued from neonatal death by deletion of the Interferon gamma ( IFNγ )... | 10.1038/nrm1714 | Shows for the first time that SOCS1 can modulate PRL signalling during pregnancy. |
10.4049/jimmunol.181.6.3755 | 122,740,467 | Abstract Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1β from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. ... | 10.1038/nrd2783 | References 42, 43, 97 and 106 identify NLRP3 as a host sensor of aluminium hydroxide, a well-known adjuvant, illustrating how NLRs influence adaptive immune responses. |
10.1242/dev.123.1.1 | 41,770,172 | In a large-scale screen, we isolated mutants displaying a specific visible phenotype in embryos or early larvae of the zebrafish, Danio rerio. Males were mutagenized with ethylnitrosourea (ENU) and F2 families of single pair matings between sibling F1 fish, heterozygous for a mutagenized genome, were raised. Egg lays w... | 10.1038/nrd1606 | References 2 and 3 describe the first large-scale genetic screens in zebrafish. These screens showed the remarkable potential of zebrafish screens and fuelled the rapid increase in the use of zebrafish for research. |
10.1073/pnas.0401496101 | 103,468,346 | Genetic screens in lower organisms, particularly those that identify modifiers of preexisting genetic defects, have been used successfully to order components of complex signaling pathways. To date, similar suppressor screens have not been used in vertebrates. To define the molecular pathways regulating platelet produc... | 10.1038/nrd1606 | In this study, a genetic screen identified mutations in c-Myb that can suppress the disease phenotype in a murine model of thrombocytopaenia. This article shows the feasibility of using genetic screens to identify novel drug targets. |
10.1242/jcs.01232 | 38,232,224 | Cells respond to a wide variety of mechanical stimuli, ranging from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. The cell membrane presents a major target of the external mechanical forces that act upon a cell, and mechanosensitive (MS) ion channels play a c... | 10.1038/nrm1890 | Discusses ion-channel involvement in mechanosensing from the viewpoint of known channels in bacterial systems. |
10.1146/annurev.biophys.35.040405.102013 | 123,850,795 | Cells can sense and transduce a broad range of mechanical forces into distinct sets of biochemical signals that ultimately regulate cellular processes, including adhesion, proliferation, differentiation, and apoptosis. Deciphering at the nanoscale the design principles by which sensory elements are integrated into stru... | 10.1038/nrm1890 | Discusses how mechanical unfolding of individual protein modules might be involved in mechanosensing in both matrix and cytoskeletal proteins. |
10.1126/science.1064829 | 104,177,027 | Adhesions between fibroblastic cells and extracellular matrix have been studied extensively in vitro, but little is known about their in vivo counterparts. Here, we characterized the composition and function of adhesions in three-dimensional (3D) matrices derived from tissues or cell culture. “3D-matrix adhesions” diff... | 10.1038/nrm1890 | Showed that the same matrix molecules produced different cellular responses when they were presented on a 2D surface versus a 3D matrix. |
10.1083/jcb.153.6.1175 | 20,751,485 | The transition of cell–matrix adhesions from the initial punctate focal complexes into the mature elongated form, known as focal contacts, requires GTPase Rho activity. In particular, activation of myosin II–driven contractility by a Rho target known as Rho-associated kinase (ROCK) was shown to be essential for focal c... | 10.1038/nrm1890 | Showed that focal adhesions grew in response to force whether or not the force was produced internally or externally. |
10.1073/pnas.072650799 | 100,815,857 | Evidence is emerging that mechanical stretching can alter the functional states of proteins. Fibronectin (Fn) is a large, extracellular matrix protein that is assembled by cells into elastic fibrils and subjected to contractile forces. Assembly into fibrils coincides with expression of biological recognition sites that... | 10.1038/nrm1890 | Provided the first direct evidence that fibronectin is actually unfolded by cell-generated forces. |
10.1126/science.1119238 | 40,284,376 | The immunological synapse is a specialized cell-cell junction that is defined by large-scale spatial patterns of receptors and signaling molecules yet remains largely enigmatic in terms of formation and function. We used supported bilayer membranes and nanometer-scale structures fabricated onto the underlying substrate... | 10.1038/nrm1890 | Showed that the immune synapse involves ordered spatial separation of membrane components that can be altered by nanofabricated substrates. |
10.1111/nph.12805 | 19,252,057 | Summary Fungi ( E umycota) form close associations with plants, with which they have co‐existed since the dawn of life on land, but their diversity in early terrestrial ecosystems is still poorly understood. We studied petrographic sections of exceptionally well‐preserved petrified plants from the 407 million yr‐old R ... | 10.1038/nrmicro.2016.149 | This study is notable because it shows that early plants were colonized by species in the Mucoromycotina and Glomeromycota, which overturns the long-held paradigm that the early endophytes were exclusively in the Glomeromycota. |
10.1126/science.1221748 | 125,099,863 | Wood is a major pool of organic carbon that is highly resistant to decay, owing largely to the presence of lignin. The only organisms capable of substantial lignin decay are white rot fungi in the Agaricomycetes, which also contains non–lignin-degrading brown rot and ectomycorrhizal species. Comparative analyses of 31 ... | 10.1038/nrmicro.2016.149 | This study maps the detailed evolution of wood-degrading enzymes by using a large set of genomes from wood-decaying fungi and shows that a key peroxidase and other enzymes that are involved in lignin decay were present in the common ancestor of the Agaricomycetes. |
10.1111/nph.13722 | 62,632,723 | Summary Ectomycorrhizal fungi are thought to have a key role in mobilizing organic nitrogen that is trapped in soil organic matter ( SOM ). However, the extent to which ectomycorrhizal fungi decompose SOM and the mechanism by which they do so remain unclear, considering that they have lost many genes encoding lignocell... | 10.1038/nrmicro.2016.149 | This works demonstrates that several ectomycorrhizal fungi are able to decompose plant litter through the use of the Fenton reaction. |
10.1038/ncomms7279 | 105,387,541 | Abstract The mutualistic association of roots with ectomycorrhizal fungi promotes plant health and is a hallmark of boreal and temperate forests worldwide. In the pre-colonization phase, before direct contact, lateral root (LR) production is massively stimulated, yet little is known about the signals exchanged during t... | 10.1038/nrmicro.2016.149 | This works suggests that volatile sesquiterpenes have a key role in the development of the ectomycorrhizal symbiosis by stimulating the formation of short roots. |
10.1073/pnas.1322671111 | 41,089,158 | Significance Plants use the hormone jasmonic acid (JA) to modulate plant:microbe interactions. Disease-causing microbes use proteins to alter host JA signaling to aid their growth in plant tissues. Beneficial symbiotic fungi, which colonize plant tissues and provide essential ecosystem services such as carbon sequestra... | 10.1038/nrmicro.2016.149 | This study shows that the symbiotic effector MiSSP7 from the ectomycorrhizal fungus L. bicolor interacts with the jasmonate co-receptor in planta to enable the development of symbiosis. |
10.1111/nph.13411 | 123,088,206 | Summary During a compatible interaction, the sebacinoid root‐associated fungi Piriformospora indica and Sebacina vermifera induce modification of root morphology and enhance shoot growth in Arabidopsis thaliana . The genomic traits common in these two fungi were investigated and compared with those of other root‐associ... | 10.1038/nrmicro.2016.149 | This works demonstrate the importance of indole-carboxylic acid derivatives as potential key players in the maintenance of a mutualistic interaction with root endophytes. |
10.1126/science.1175371 | 125,297,532 | Lysine Acetylation Catalog Covalent posttranslational modification is an essential cellular regulatory mechanism by which the activity of proteins can be controlled. Advances in mass spectrometry made it possible for Choudhary et al. (p. 834 , published online 16 July) to assess the prevalence of lysine acetylation thr... | 10.1038/nrm.2016.143 | A large-scale, high-resolution proteomic screen that identified over 3,500 acetylated Lys sites in human cells. |
10.1126/science.288.5470.1422 | 62,054,095 | TFIID is a large multiprotein complex that initiates assembly of the transcription machinery. It is unclear how TFIID recognizes promoters in vivo when templates are nucleosome-bound. Here, it is shown that TAF II 250, the largest subunit of TFIID, contains two tandem bromodomain modules that bind selectively to multip... | 10.1038/nrm.2016.143 | The first crystal structure of a tandem BRD module from TAF1, which established the rationale for the simultaneous engagement of multiple acetylated histone peptides. |
10.1126/science.1092436 | 83,554,355 | Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type–specific fashion. We used this method to purify the label-retaining cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells rar... | 10.1038/nrm3272 | Describes the generation of a mouse model combining two transgenes to fluorescently tag slow-cycling cells, which has been widely applied to other systems, including the HSCs as in references 26 and 80.Also reports the transcriptional profiling that identified genes preferentially expressed by HFSCs. |
10.1126/science.1066700 | 38,960,117 | Stem cells, which regenerate tissue by producing differentiating cells, also produce cells that renew the stem cell population. Signals from regulatory microenvironments (niches) are thought to cause stem cells to retain self-renewing potential. However, the molecular characterization of niches remains an important goa... | 10.1038/nrm3272 | References 17–19 demonstrate the existence of niches for D. melanogaster germline stem cells and describe the signalling events involved. References 17 identifies 'cap cells' as key GSC niche components in the ovary. References 18 and 19 define the hub as the niche for testis GSCs. |
10.1242/dev.057364 | 102,208,136 | To function properly, tissue-specific stem cells must reside in a niche. The Drosophila testis niche is one of few niches studied in vivo. Here, a single niche, comprising ten hub cells, maintains both germline stem cells (GSC) and somatic stem cells (CySC). Here, we show that lines is an essential CySC factor. Surpris... | 10.1038/nrm3272 | References 35 and 37 demonstrate that, under some circumstances, progeny of CySCs can differentiate into hub cells. Reference 35 observes this contribution during steady state. Reference 37 observes this conversion mainly when the CySCs carry mutations in the lines gene. |
10.1126/science.1213214 | 62,279,733 | Two niches with distinct characteristics work in tandem. | 10.1038/nrm3272 | Applying similar strategies to reference 25, references 76–78 show that slow-cycling cells located at the +4 position are also ISCs. Reference 78 shows that the two ISC populations are interchangeable. |
10.1084/jem.20101688 | 81,541,294 | Hematopoietic stem cells (HSCs) reside in specialized bone marrow (BM) niches regulated by the sympathetic nervous system (SNS). Here, we have examined whether mononuclear phagocytes modulate the HSC niche. We defined three populations of BM mononuclear phagocytes that include Gr-1hi monocytes (MOs), Gr-1lo MOs, and ma... | 10.1038/nrm3272 | References 110 and 111 show that macrophages, which are a type of HSC progeny of the myeloid lineage, function in retaining HSCs in their bone marrow niche. |
10.1126/science.1078694 | 81,557,601 | Heterochromatin protein 1 (HP1β), a key component of condensed DNA, is strongly implicated in gene silencing and centromeric cohesion. Heterochromatin has been considered a static structure, stabilizing crucial aspects of nuclear organization and prohibiting access to transcription factors. We demonstrate here, by fluo... | 10.1038/nrg2008 | References 27 and 28 demonstrated that the heterochromatin protein HP1 is highly dynamic, even in heterochromatin domains, which are generally perceived to be highly stable. |
10.1126/science.1060118 | 20,680,067 | The assembly of higher order chromatin structures has been linked to the covalent modifications of histone tails. We provide in vivo evidence that lysine 9 of histone H3 (H3 Lys 9 ) is preferentially methylated by the Clr4 protein at heterochromatin-associated regions in fission yeast. Both the conserved chromo- and SE... | 10.1038/nrg2008 | This paper demonstrated that methylation of H3K9 is crucial for recruitment of Swi6/HP1 to heterochromatic loci. |
10.1126/science.1076466 | 103,681,651 | The higher-order assembly of chromatin imposes structural organization on the genetic information of eukaryotes and is thought to be largely determined by posttranslational modification of histone tails. Here, we study a 20-kilobase silent domain at the mating-type region of fission yeast as a model for heterochromatin... | 10.1038/nrg2008 | This paper established a link between RNAi and heterochromatin assembly in fission yeast, and showed that heterochromatin assembly that is nucleated at a repeat element can spread in a manner that is dependent upon Swi6/HP1. |
10.1126/science.1074973 | 125,117,813 | Eukaryotic heterochromatin is characterized by a high density of repeats and transposons, as well as by modified histones, and influences both gene expression and chromosome segregation. In the fission yeast Schizosaccharomyces pombe , we deleted the argonaute, dicer, and RNA-dependent RNA polymerase gene homologs, whi... | 10.1038/nrg2008 | This paper demonstrated that the RNAi machinery is required for transcriptional silencing and heterochromatin formation at the centromeres in fission yeast. |
10.1126/science.1092653 | 41,519,514 | Genes normally resident in euchromatic domains are silenced when packaged into heterochromatin, as exemplified in Drosophila melanogaster by position effect variegation (PEV). Loss-of-function mutations resulting in suppression of PEV have identified critical components of heterochromatin, including proteins HP1, HP2, ... | 10.1038/nrg2008 | This study demonstrated that the RNAi machinery is required for silencing and heterochromatin formation in D. melanogaster |
10.1126/science.1079695 | 125,121,467 | Proteins of the ARGONAUTE family are important in diverse posttranscriptional RNA-mediated gene-silencing systems as well as in transcriptional gene silencing in Drosophila and fission yeast and in programmed DNA elimination in Tetrahymena . We cloned ARGONAUTE4 ( AGO4 ) from a screen for mutants that suppress silencin... | 10.1038/nrg2008 | These authors established that the RNAi machinery is required for heterochromatic gene silencing and control of transposable elements in A. thaliana |
10.1126/science.1114955 | 125,119,184 | In Schizosaccharomyces pombe , the RNA interference (RNAi) machinery converts pericentromeric transcripts into small interfering RNAs (siRNAs) and is required for the assembly of pericentromeric heterochromatin. Here we describe a mutation in the second largest subunit of RNA polymerase II (RNAPII). Both wild-type and ... | 10.1038/nrg2008 | References 75 and 76 showed that mutations in RNA Pol II subunits affect RNAi-mediated heterochromatin assembly at fission yeast centromeres. |
10.1126/science.1093686 | 125,118,973 | RNA interference (RNAi) is a widespread silencing mechanism that acts at both the posttranscriptional and transcriptional levels. Here, we describe the purification of an RNAi effector complex termed RITS (RNA-induced initiation of transcriptional gene silencing) that is required for heterochromatin assembly in fission... | 10.1038/nrg2008 | This paper reported the identification of the RITS complex, which is involved in RNAi-mediated heterochromatin assembly and silencing in fission yeast. |
10.1126/science.1088755 | 122,979,763 | An ultrasensitive method for detecting protein analytes has been developed. The system relies on magnetic microparticle probes with antibodies that specifically bind a target of interest [prostate-specific antigen (PSA) in this case] and nanoparticle probes that are encoded with DNA that is unique to the protein target... | 10.1038/nrg1892 | Introduces the BCA method for the highly sensitive detection of proteins. Subsequent papers extend the use of the method to disease diagnosis. |
10.1126/science.1102629 | 123,951,771 | The translation of nucleic acid libraries into corresponding synthetic compounds would enable selection and amplification principles to be applied to man-made molecules. We used multistep DNA-templated organic synthesis to translate libraries of DNA sequences, each containing three “codons,” into libraries of sequence-... | 10.1038/nrg1892 | Illustrates the use of DTS to create a pool of molecules from which those with new functional properties might be selected. |
10.1126/science.7973651 | 20,487,984 | The tools of molecular biology were used to solve an instance of the directed Hamiltonian path problem. A small graph was encoded in molecules of DNA, and the "operations" of the computation were performed with standard protocols and enzymes. This experiment demonstrates the feasibility of carrying out computations at ... | 10.1038/nrg1892 | Introduces the principle of DNA computation by solving a tiny combinatorial problem in a test tube. |
10.1126/science.1089389 | 62,609,312 | A DNA nanostructure consisting of four four-arm junctions oriented with a square aspect ratio was designed and constructed. Programmable self-assembly of 4 × 4 tiles resulted in two distinct lattice morphologies: uniform-width nanoribbons and two-dimensional nanogrids, which both display periodic square cavities. Perio... | 10.1038/nrg1892 | Describes the construction and use of 2D DNA lattices for the organization of proteins, and the construction of DNA nanotubes. |
10.1084/jem.188.8.1511 | 61,288,678 | Susceptibility to multiple sclerosis is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 (DRB1*1501) haplotype. The structure of HLA-DR2 was determined with a bound peptide from human myelin basic protein (MBP) that is immunodominant for human MBP-specific T cells. Residues of MBP peptide that a... | 10.1038/nri1805 | This paper reports the crystal structure of HLA-DR2b in complex with the multiple-sclerosis-associated immunodominant epitope from MBP described in reference 4. When presented in the context of HLA-DR2b, this epitope is known to elicit disease-causing T-cell responses. |
10.1073/pnas.0308458100 | 102,312,226 | The MHC class II molecule DQ0602 confers strong susceptibility to narcolepsy but dominant protection against type 1 diabetes. The crystal structure of DQ0602 reveals the molecular features underlying these contrasting genetic properties. Structural comparisons to homologous DQ molecules with differential disease associ... | 10.1038/nri1805 | This structural analysis of HLA-DQ6.2 reveals features of the peptide-binding groove that correlate with susceptibility to narcolepsy and protection against type 1 diabetes. |
10.1073/pnas.0306885101 | 59,724,349 | Celiac disease, also known as celiac sprue, is a gluten-induced autoimmune-like disorder of the small intestine, which is strongly associated with HLA-DQ2. The structure of DQ2 complexed with an immunogenic epitope from gluten, QLQPFPQPELPY, has been determined to 2.2-Å resolution by x-ray crystallography. The glutamat... | 10.1038/nri1805 | The structure of HLA-DQ2 in complex with a gluten-derived peptide shows how MHC class II peptide-binding-groove characteristics allow the binding of peptides from atypical protein sequences, in this case gliadin, leading to susceptibility to coeliac disease. |
10.1046/j.1365-2567.1999.00772.x | 79,418,866 | Normal immunological memory is thought to be underpinned by T lymphocytes. However, in rheumatoid arthritis there are indications that T‐lymphocyte control has been subverted by self‐perpetuating B lymphocytes. Potential mechanisms in other autoimmune states are less clear, but a number of observations suggest that mis... | 10.1038/nri1838 | This review outlines the concept of self-perpetuating autoreactive B cells, on which B-cell-depletion therapy in rheumatoid arthritis was based. |
10.1002/art.11181 | 82,011,420 | Abstract Objective To explore the changes in serologic variables and clinical disease activity following B lymphocyte depletion in 22 patients with rheumatoid arthritis (RA). Methods B lymphocyte depletion was attained using combination therapy based on the monoclonal anti‐CD20 antibody rituximab. Levels of a serologic... | 10.1038/nri1838 | This paper describes the pharmacodynamics of B-cell depletion in rheumatoid arthritis in terms of circulating B-cell numbers, autoantibody levels and clinical response. |
10.1084/jem.173.2.487 | 123,401,454 | Using Epstein-Barr virus B cell clones and antigen-specific T cell clones, we asked how antigen-antibody complexes are handled by B cells. We found that the only B cells capable of efficient presentation of antigen-antibody complexes are those that bind the complexes via membrane immunoglobulin, i.e., rheumatoid factor... | 10.1038/nri1838 | This paper provides perhaps the first clear in vitro demonstration that B cells and T cells of different affinities can interact in unusual ways. |
10.4049/jimmunol.174.2.817 | 83,275,823 | Abstract B cell immunotherapy has emerged as a mainstay in the treatment of lymphomas and autoimmune diseases. Although the microenvironment has recently been demonstrated to play critical roles in B cell homeostasis, its contribution to immunotherapy is unknown. To analyze the in vivo factors that regulate mechanisms ... | 10.1038/nri1838 | This paper provides detailed recent insights into the mechanisms of B-cell killing by rituximab. |
10.1182/blood-2015-09-618538 | 18,761,574 | Abstract Sickle cell disease (SCD) is a severe genetic blood disorder characterized by hemolytic anemia, episodic vaso-occlusion, and progressive organ damage. Current management of the disease remains symptomatic or preventative. Specific treatment targeting major complications such as vaso-occlusion is still lacking.... | 10.1038/nrdp.2018.10 | This is an updated review of the principal adhesive pathways involved in SCD vaso-occlusion. |
10.1182/blood-2004-08-3156 | 125,059,923 | Abstract It is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC–specific inhibitory receptors, yet... | 10.1038/nri1863 | This report was the first to show in normal animals the existence of self-tolerant NK cells that lack inhibitory receptors specific for self MHC class I molecules, as well as to show that these NK cells (similar to all NK cells from MHC-class-I-deficient mice) show dampened responses to stimulatory ligands and tumour c... |
10.1126/science.2814488 | 97,927,782 | Rejection of bone marrow grafts in irradiated mice is mediated by natural killer (NK) cells and is controlled by genes linked to the major histocompatibility complex (MHC). It has, however, not been possible to identify the genes or their products. An MHC class I (D d ) transgene introduced in C57BL donors prevented th... | 10.1038/nri1863 | This study shows that providing H2 b mice with an allogeneic MHC class I transgene ( H2-D d ) is sufficient to enable their NK cells to attack parental (H2 b ) cells. The capacity of the transgenic cells to attack otherwise identical parental cells indicated that there must be a tolerance mechanism that prevents such r... |
10.1073/pnas.88.22.10332 | 59,730,311 | The role of major histocompatibility complex (MHC) class I expression in control of the sensitivity of normal cells to natural killer (NK) cells was studied by the use of mutant mice made deficient for expression of beta 2-microglobulin (beta 2m) through homologous recombination in embryonal stem cells. T-cell blasts f... | 10.1038/nri1863 | References 20–22 show that NK cells develop in MHC-class-I-deficient mice (β 2 m-deficient mice) and that, despite the absence of MHC-class-I-specific inhibitory molecules, these NK cells are self-tolerant. In addition, these NK cells show impaired killing of certain tumour target cells and fail to reject allogeneic bo... |
10.1182/blood-2005-01-0357 | 97,572,705 | Abstract Natural killer (NK) cells must be able to eliminate infected and transformed cells while remaining tolerant of normal cells. NK-cell self-tolerance is thought to be maintained by self-major histocompatibility complex (MHC) class I recognition; however, there are examples where NK cells are not regulated by MHC... | 10.1038/nri1863 | Using mice with mutations in CD48, which is a ligand for the receptor 2B4, this paper shows that 2B4 provides a potent inhibitory signal to NK cells. The possibility that this inhibitory interaction has a role in NK-cell self-tolerance is discussed. |
10.4049/jimmunol.158.4.1628 | 139,052,439 | Abstract NK cells in normal mice reject bone marrow transplants from class I-deficient mice. In contrast, class I-deficient mice do not reject autologous cells, suggesting that NK cell tolerance is acquired. We employed fetal liver irradiation chimeras to assess two potential mechanisms that could account for the toler... | 10.1038/nri1863 | In this paper, fetal liver chimeras were studied in which mixtures of normal and MHC-class-I-deficient haematopoietic cells differentiated in either MHC-class-I-expressing or MHC-class-I-deficient hosts. The results show that body cells that lack expression of MHC class I molecules dominantly induce tolerance of NK cel... |
10.1084/jem.186.3.353 | 45,024,665 | We have studied natural killer (NK) cell tolerance in a major histocompatibility complex (MHC) class I transgenic line, DL6, in which the transgene product was expressed on only a fraction of blood cells. In contrast with transgenic mice expressing the same transgene in all cells, NK cells from mosaic mice failed to re... | 10.1038/nri1863 | In this study, mice that express an MHC class I ( H2-D d ) transgene in a mosaic manner (that is, at the surface of some cells but not others) were examined. The results show that body cells that lack an MHC class I molecule dominantly induce tolerance of NK cells, despite the presence of cells that do express MHC clas... |
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