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These results showed broad and consistent representation of major immune lineages in our dataset.
|
[
{
"end": 81,
"label": "CellType",
"start": 66,
"text": "immune lineages"
}
] |
Single_Cell
|
Source paper: PMC12396968
We next analyzed the subset composition and heterogeneity for each immune cell lineage across tissues based on the MMoCHi annotations above.
|
[
{
"end": 114,
"label": "CellType",
"start": 95,
"text": "immune cell lineage"
},
{
"end": 129,
"label": "Tissue",
"start": 122,
"text": "tissues"
}
] |
Single_Cell
|
T lymphocytes (610,429 cells) comprised low-frequency γδ T cells, which develop early in ontogeny, and predominant αβ T cells (Fig. 2a,b and Supplementary Fig. 2 ).
|
[
{
"end": 13,
"label": "CellType",
"start": 0,
"text": "T lymphocytes"
},
{
"end": 64,
"label": "CellType",
"start": 53,
"text": " γδ T cells"
},
{
"end": 125,
"label": "CellType",
"start": 115,
"text": "αβ T cells"
}
] |
Single_Cell
|
CD4 and CD8 T cells (αβ TCR ) were subdivided into naive (T N ), terminal effector (T EMRA ) and memory subsets, including effector-memory (T EM ), central memory (T CM ) and T RM , along with CD4 regulatory T cells (T reg ) (Fig. 2a,b ).
|
[
{
"end": 3,
"label": "CellType",
"start": 0,
"text": "CD4"
},
{
"end": 19,
"label": "CellType",
"start": 8,
"text": "CD8 T cells"
},
{
"end": 56,
"label": "CellType",
"start": 51,
"text": "naive"
},
{
"end": 61,
"label": "CellType",
"start": 58,
"text": "T N"
},
{
"end": 82,
"label": "CellType",
"start": 65,
"text": "terminal effector"
},
{
"end": 90,
"label": "CellType",
"start": 84,
"text": "T EMRA"
},
{
"end": 111,
"label": "CellType",
"start": 97,
"text": "memory subsets"
},
{
"end": 138,
"label": "CellType",
"start": 123,
"text": "effector-memory"
},
{
"end": 144,
"label": "CellType",
"start": 140,
"text": "T EM"
},
{
"end": 162,
"label": "CellType",
"start": 148,
"text": "central memory"
},
{
"end": 168,
"label": "CellType",
"start": 164,
"text": "T CM"
},
{
"end": 179,
"label": "CellType",
"start": 175,
"text": "T RM"
},
{
"end": 215,
"label": "CellType",
"start": 193,
"text": "CD4 regulatory T cells"
},
{
"end": 222,
"label": "CellType",
"start": 217,
"text": "T reg"
}
] |
Single_Cell
|
Surface proteins were essential for identifying T cell subsets that were not fully resolved by scRNA-seq (Fig. 2b and Supplementary Fig. 3 ), as shown before .
|
[
{
"end": 62,
"label": "CellType",
"start": 48,
"text": "T cell subsets"
}
] |
Single_Cell
|
For example, surface CD45RA expression was required to distinguish CD45RA T N cells from CD45RA T CM cells and CD45RA T EM cells from CD45RA T EMRA cells, and surface γδ or αβ T cell receptor (TCR) expression to accurately identify γδ T cells from CD8 T cells, which can express TRDC (Fig. 2b ).
|
[
{
"end": 83,
"label": "CellType",
"start": 67,
"text": "CD45RA T N cells"
},
{
"end": 106,
"label": "CellType",
"start": 89,
"text": "CD45RA T CM cells"
},
{
"end": 128,
"label": "CellType",
"start": 111,
"text": "CD45RA T EM cells"
},
{
"end": 153,
"label": "CellType",
"start": 134,
"text": "CD45RA T EMRA cells"
},
{
"end": 242,
"label": "CellType",
"start": 232,
"text": "γδ T cells"
},
{
"end": 259,
"label": "CellType",
"start": 248,
"text": "CD8 T cells"
}
] |
Single_Cell
|
In addition, T RM cells were distinguished from T EM cells based on surface expression of CD69, CD103 and/or CD49a (Fig. 2b and Supplementary Fig. 3 ).
|
[
{
"end": 23,
"label": "CellType",
"start": 13,
"text": "T RM cells"
},
{
"end": 58,
"label": "CellType",
"start": 48,
"text": "T EM cells"
}
] |
Single_Cell
|
T cell subsets were differentially distributed across sites; CD4 T N , CD8 T N and CD4 T CM cells were enriched in blood and multiple LN, CD4 T reg cells were enriched in LN, while CD4 and CD8 T RM cells predominated in JEJ and were present at lower frequencies in lungs, spleen and LN (Fig. 2a,b ).
|
[
{
"end": 120,
"label": "Tissue",
"start": 115,
"text": "blood"
},
{
"end": 270,
"label": "Tissue",
"start": 265,
"text": "lungs"
},
{
"end": 278,
"label": "Tissue",
"start": 272,
"text": "spleen"
},
{
"end": 14,
"label": "CellType",
"start": 0,
"text": "T cell subsets"
},
{
"end": 68,
"label": "CellType",
"start": 61,
"text": "CD4 T N"
},
{
"end": 78,
"label": "CellType",
"start": 71,
"text": "CD8 T N"
},
{
"end": 97,
"label": "CellType",
"start": 83,
"text": "CD4 T CM cells"
},
{
"end": 136,
"label": "Tissue",
"start": 125,
"text": "multiple LN"
},
{
"end": 153,
"label": "CellType",
"start": 138,
"text": "CD4 T reg cells"
},
{
"end": 173,
"label": "Tissue",
"start": 171,
"text": "LN"
},
{
"end": 184,
"label": "CellType",
"start": 181,
"text": "CD4"
},
{
"end": 203,
"label": "CellType",
"start": 189,
"text": "CD8 T RM cells"
},
{
"end": 223,
"label": "Tissue",
"start": 220,
"text": "JEJ"
},
{
"end": 285,
"label": "Tissue",
"start": 283,
"text": "LN"
}
] |
Single_Cell
|
T EMRA cells were mostly CD8 and enriched in the BM and spleen and, to a lesser extent, in lungs, while T EM cells were distributed across most sites (Fig. 2a,b ).
|
[
{
"end": 96,
"label": "Tissue",
"start": 91,
"text": "lungs"
},
{
"end": 62,
"label": "Tissue",
"start": 56,
"text": "spleen"
},
{
"end": 12,
"label": "CellType",
"start": 0,
"text": "T EMRA cells"
},
{
"end": 28,
"label": "CellType",
"start": 25,
"text": "CD8"
},
{
"end": 51,
"label": "Tissue",
"start": 49,
"text": "BM"
},
{
"end": 114,
"label": "CellType",
"start": 104,
"text": "T EM cells"
}
] |
Single_Cell
|
Mucosal-associated invariant T (MAIT) cells, distinguished by TRAV1.2 expression, CD161 and other markers , were predominantly found in the spleen, BM and lungs (Fig. 2a,b ).
|
[
{
"end": 160,
"label": "Tissue",
"start": 155,
"text": "lungs"
},
{
"end": 146,
"label": "Tissue",
"start": 140,
"text": "spleen"
},
{
"end": 43,
"label": "CellType",
"start": 0,
"text": "Mucosal-associated invariant T (MAIT) cells"
},
{
"end": 150,
"label": "Tissue",
"start": 148,
"text": "BM"
}
] |
Single_Cell
|
TCR clonal analysis provided additional correlative evidence for subset delineation and tissue distribution (for example, with the highest clonality observed in the T EMRA subset, as previously described ) (Supplementary Fig. 2 ).
|
[
{
"end": 178,
"label": "CellType",
"start": 165,
"text": "T EMRA subset"
}
] |
Single_Cell
|
Source paper: PMC12396968
Innate lymphocytes (130,414 cells) were predominantly mature CD56 CD16 NK cells expressing cytolytic markers ( KLRF1 , GZMB ) and enriched in blood, BM and lungs (Fig. 2c,d ).
|
[
{
"end": 175,
"label": "Tissue",
"start": 170,
"text": "blood"
},
{
"end": 189,
"label": "Tissue",
"start": 184,
"text": "lungs"
},
{
"end": 46,
"label": "CellType",
"start": 28,
"text": "Innate lymphocytes"
},
{
"end": 107,
"label": "CellType",
"start": 82,
"text": "mature CD56 CD16 NK cells"
},
{
"end": 179,
"label": "Tissue",
"start": 177,
"text": "BM"
}
] |
Single_Cell
|
Immature CD56 CD16 NK cells were present at lower frequencies across most tissues (Fig. 2c,d ).
|
[
{
"end": 27,
"label": "CellType",
"start": 0,
"text": "Immature CD56 CD16 NK cells"
},
{
"end": 81,
"label": "Tissue",
"start": 74,
"text": "tissues"
}
] |
Single_Cell
|
We detected low frequencies of ILCs consisting largely of CD16 NCR2 IL7R ILC1s with high expression of tissue residency markers (CD69, CD49a, CD103) enriched in JEJ, and IL7R KIT RORC ILC3 (ref. )
|
[
{
"end": 35,
"label": "CellType",
"start": 31,
"text": "ILCs"
},
{
"end": 78,
"label": "CellType",
"start": 58,
"text": "CD16 NCR2 IL7R ILC1s"
},
{
"end": 164,
"label": "Tissue",
"start": 161,
"text": "JEJ"
},
{
"end": 188,
"label": "CellType",
"start": 170,
"text": "IL7R KIT RORC ILC3"
}
] |
Single_Cell
|
found in LN, spleen and JEJ (Fig. 2c,d ).
|
[
{
"end": 19,
"label": "Tissue",
"start": 13,
"text": "spleen"
},
{
"end": 11,
"label": "Tissue",
"start": 9,
"text": "LN"
},
{
"end": 27,
"label": "Tissue",
"start": 24,
"text": "JEJ"
}
] |
Single_Cell
|
Putative CD127 CD62L TCF7 NK/ILC precursors, resembling CD56 CD16 NK and ILC3s , were enriched in blood but present in all tissues (Fig. 2c,d ).
|
[
{
"end": 103,
"label": "Tissue",
"start": 98,
"text": "blood"
},
{
"end": 43,
"label": "CellType",
"start": 0,
"text": "Putative CD127 CD62L TCF7 NK/ILC precursors"
},
{
"end": 68,
"label": "CellType",
"start": 56,
"text": "CD56 CD16 NK"
},
{
"end": 78,
"label": "CellType",
"start": 73,
"text": "ILC3s"
},
{
"end": 130,
"label": "Tissue",
"start": 123,
"text": "tissues"
}
] |
Single_Cell
|
Source paper: PMC12396968
B cells (272,162 cells) were classified into 6 subsets largely confined to lymphoid organs (Fig. 2e,f ), including IgD naive B cells, CD27 memory B cells, germinal center B cells expressing AICDA (encoding activation-induced adenosine deaminase, which mediates somatic mutation and class switch recombination ), plasma cells expressing immunoglobulin genes and SDC1 (CD138) and plasmablasts expressing proliferation markers ( MKI67 , TOP2A ) (Fig. 2f ).
|
[
{
"end": 35,
"label": "CellType",
"start": 28,
"text": "B cells"
},
{
"end": 118,
"label": "Tissue",
"start": 103,
"text": "lymphoid organs"
},
{
"end": 160,
"label": "CellType",
"start": 143,
"text": "IgD naive B cells"
},
{
"end": 181,
"label": "CellType",
"start": 162,
"text": "CD27 memory B cells"
},
{
"end": 206,
"label": "CellType",
"start": 183,
"text": "germinal center B cells"
},
{
"end": 352,
"label": "CellType",
"start": 340,
"text": "plasma cells"
},
{
"end": 418,
"label": "CellType",
"start": 406,
"text": "plasmablasts"
}
] |
Single_Cell
|
CD11c memory B cells expressing TBX21 (encoding the transcription factor T-BET) resembled ‘atypical B cells’ and were found at low frequencies in spleen and BM (Fig. 2e,f ).
|
[
{
"end": 152,
"label": "Tissue",
"start": 146,
"text": "spleen"
},
{
"end": 20,
"label": "CellType",
"start": 0,
"text": "CD11c memory B cells"
},
{
"end": 107,
"label": "CellType",
"start": 91,
"text": "atypical B cells"
},
{
"end": 159,
"label": "Tissue",
"start": 157,
"text": "BM"
}
] |
Single_Cell
|
Variable frequencies of memory B cells in LN and spleen expressed CD69 (Fig. 2e,f ), denoting tissue residency .
|
[
{
"end": 55,
"label": "Tissue",
"start": 49,
"text": "spleen"
},
{
"end": 38,
"label": "CellType",
"start": 24,
"text": "memory B cells"
},
{
"end": 44,
"label": "Tissue",
"start": 42,
"text": "LN"
}
] |
Single_Cell
|
Plasma cells expressing IgA were enriched in the JLP, while IgG plasmablasts were enriched in lymphoid organs (Fig. 2e,f ).
|
[
{
"end": 12,
"label": "CellType",
"start": 0,
"text": "Plasma cells"
},
{
"end": 52,
"label": "Tissue",
"start": 49,
"text": "JLP"
},
{
"end": 76,
"label": "CellType",
"start": 60,
"text": "IgG plasmablasts"
},
{
"end": 109,
"label": "Tissue",
"start": 94,
"text": "lymphoid organs"
}
] |
Single_Cell
|
B cell receptor (BCR) analysis indicated that plasmablasts exhibited the highest clonal expansion across lymphoid sites, while memory B cells and plasma (but not naive) cells expressed mutated BCR (Supplementary Fig. 4 ).
|
[
{
"end": 58,
"label": "CellType",
"start": 46,
"text": "plasmablasts"
},
{
"end": 119,
"label": "Tissue",
"start": 105,
"text": "lymphoid sites"
},
{
"end": 141,
"label": "CellType",
"start": 127,
"text": "memory B cells"
},
{
"end": 174,
"label": "CellType",
"start": 146,
"text": "plasma (but not naive) cells"
}
] |
Single_Cell
|
Source paper: PMC12396968
Myeloid lineage cells (225,268 cells) comprised C1QA MS4A7 macrophages, FCN1 CD14 classical and FCN1 FCGR3A non-classical monocytes and DC subsets, including CLEC9A DC1, CLEC10A DC2, CCR7 migratory DCs and CD123 LILRA4 plasmacytoid DCs (pDCs) (Fig. 2g,h ).
|
[
{
"end": 49,
"label": "CellType",
"start": 28,
"text": "Myeloid lineage cells"
},
{
"end": 98,
"label": "CellType",
"start": 76,
"text": "C1QA MS4A7 macrophages"
},
{
"end": 119,
"label": "CellType",
"start": 100,
"text": "FCN1 CD14 classical"
},
{
"end": 159,
"label": "CellType",
"start": 124,
"text": "FCN1 FCGR3A non-classical monocytes"
},
{
"end": 174,
"label": "CellType",
"start": 164,
"text": "DC subsets"
},
{
"end": 196,
"label": "CellType",
"start": 186,
"text": "CLEC9A DC1"
},
{
"end": 209,
"label": "CellType",
"start": 198,
"text": "CLEC10A DC2"
},
{
"end": 229,
"label": "CellType",
"start": 211,
"text": "CCR7 migratory DCs"
},
{
"end": 263,
"label": "CellType",
"start": 234,
"text": "CD123 LILRA4 plasmacytoid DCs"
},
{
"end": 269,
"label": "CellType",
"start": 265,
"text": "pDCs"
}
] |
Single_Cell
|
Classical monocytes were most abundant in blood, while non-classical monocytes were found mainly in BM and lung (Fig. 2g,h ).
|
[
{
"end": 47,
"label": "Tissue",
"start": 42,
"text": "blood"
},
{
"end": 111,
"label": "Tissue",
"start": 107,
"text": "lung"
},
{
"end": 19,
"label": "CellType",
"start": 0,
"text": "Classical monocytes"
},
{
"end": 78,
"label": "CellType",
"start": 55,
"text": "non-classical monocytes"
},
{
"end": 102,
"label": "Tissue",
"start": 100,
"text": "BM"
}
] |
Single_Cell
|
DCs were found at low frequency across all tissues; pDCs were enriched in the BM, migratory DCs in the LNs, while DC2s were found mainly in the LNs and JEJ (Fig. 2g,h ).
|
[
{
"end": 3,
"label": "CellType",
"start": 0,
"text": "DCs"
},
{
"end": 50,
"label": "Tissue",
"start": 43,
"text": "tissues"
},
{
"end": 56,
"label": "CellType",
"start": 52,
"text": "pDCs"
},
{
"end": 80,
"label": "Tissue",
"start": 78,
"text": "BM"
},
{
"end": 95,
"label": "CellType",
"start": 82,
"text": "migratory DCs"
},
{
"end": 106,
"label": "Tissue",
"start": 103,
"text": "LNs"
},
{
"end": 118,
"label": "CellType",
"start": 114,
"text": "DC2s"
},
{
"end": 147,
"label": "Tissue",
"start": 144,
"text": "LNs"
},
{
"end": 155,
"label": "Tissue",
"start": 152,
"text": "JEJ"
}
] |
Single_Cell
|
Macrophages were found predominantly in the lung and at low frequencies in the BM, spleen, LNs and JEJ (Fig. 2h ).
|
[
{
"end": 11,
"label": "CellType",
"start": 0,
"text": "Macrophages"
},
{
"end": 48,
"label": "Tissue",
"start": 44,
"text": "lung"
},
{
"end": 89,
"label": "Tissue",
"start": 83,
"text": "spleen"
},
{
"end": 81,
"label": "Tissue",
"start": 79,
"text": "BM"
},
{
"end": 94,
"label": "Tissue",
"start": 91,
"text": "LNs"
},
{
"end": 102,
"label": "Tissue",
"start": 99,
"text": "JEJ"
}
] |
Single_Cell
|
Source paper: PMC12396968
Immune cell subset composition for the lineages above in blood, lymphoid organs and mucosal sites was specific to the site and conserved across donors (Fig. 2i and Extended Data Fig. 2 ).
|
[
{
"end": 90,
"label": "Tissue",
"start": 85,
"text": "blood"
},
{
"end": 107,
"label": "Tissue",
"start": 92,
"text": "lymphoid organs"
},
{
"end": 125,
"label": "Tissue",
"start": 112,
"text": "mucosal sites"
},
{
"end": 47,
"label": "CellType",
"start": 28,
"text": "Immune cell subset "
}
] |
Single_Cell
|
We defined additional subset heterogeneity based on RNA expression, identifying proliferating cells across lineages and functional subsets for CD8 T EM cells and CD8 T EMRA cells, also with tissue-specific distribution (Supplementary Figs. 5 and 6 ).
|
[
{
"end": 99,
"label": "CellType",
"start": 80,
"text": "proliferating cells"
},
{
"end": 157,
"label": "CellType",
"start": 143,
"text": "CD8 T EM cells"
},
{
"end": 178,
"label": "CellType",
"start": 162,
"text": "CD8 T EMRA cells"
}
] |
Single_Cell
|
This comprehensive, annotated map of immune cells across tissues can serve as a reference for future analysis, and we provided pre-trained models for label transfer of our cell-type annotation in the popV framework (Supplementary Fig. 7 ).
|
[
{
"end": 49,
"label": "CellType",
"start": 37,
"text": "immune cells"
},
{
"end": 64,
"label": "Tissue",
"start": 57,
"text": "tissues"
}
] |
Single_Cell
|
This subset analysis showed consistent, tissue-specific composition between sites.
|
[] |
Single_Cell
|
Source paper: PMC12396968
To understand the influence of tissue localization on gene expression, we performed a two-step differential expression (DE) analysis.
|
[] |
Single_Cell
|
First, we compared the major immune lineages (CD8 T cells, CD4 T cells, γδ/ΜΑΙΤ cells, myeloid cells, NK/ILC and B cells) within each site (for example, blood, BM, spleen, LN, lung, JEJ) versus the other sites using pseudobulked linear mixed modeling (LMM), controlling for covariates (for example, sex, CMV serostatus) (Fig. 3a and Supplementary Tables 4 and 5 ).
|
[
{
"end": 120,
"label": "CellType",
"start": 113,
"text": "B cells"
},
{
"end": 158,
"label": "Tissue",
"start": 153,
"text": "blood"
},
{
"end": 180,
"label": "Tissue",
"start": 176,
"text": "lung"
},
{
"end": 170,
"label": "Tissue",
"start": 164,
"text": "spleen"
},
{
"end": 44,
"label": "CellType",
"start": 23,
"text": "major immune lineages"
},
{
"end": 57,
"label": "CellType",
"start": 46,
"text": "CD8 T cells"
},
{
"end": 70,
"label": "CellType",
"start": 59,
"text": "CD4 T cells"
},
{
"end": 85,
"label": "CellType",
"start": 72,
"text": "γδ/ΜΑΙΤ cells"
},
{
"end": 100,
"label": "CellType",
"start": 87,
"text": "myeloid cells"
},
{
"end": 108,
"label": "CellType",
"start": 102,
"text": "NK/ILC"
},
{
"end": 162,
"label": "Tissue",
"start": 160,
"text": "BM"
},
{
"end": 174,
"label": "Tissue",
"start": 172,
"text": "LN"
},
{
"end": 185,
"label": "Tissue",
"start": 182,
"text": "JEJ"
}
] |
Single_Cell
|
We identified 13 clusters from significantly differentially expressed genes (DEGs) (C1–13) grouped by lineage and/or tissue (Fig. 3b and Supplementary Table 6 ).
|
[
{
"end": 123,
"label": "Tissue",
"start": 117,
"text": "tissue"
},
{
"end": 109,
"label": "CellType",
"start": 102,
"text": "lineage"
}
] |
Single_Cell
|
We then conducted a similar across-tissue DE analysis for each subset and evaluated whether these signatures were expressed by individual subsets within a lineage using gene set enrichment analysis (GSEA) (Fig. 3a ).
|
[
{
"end": 162,
"label": "CellType",
"start": 155,
"text": "lineage"
}
] |
Single_Cell
|
To visualize effect sizes, determine the contribution of compositional differences and identify tissue-specific signatures across lineages, we integrated this analysis with subset frequencies within a tissue, fold changes (FC) compared to the other sites and the average expression of gene clusters by subset (Fig. 3c–h , Extended Data Fig. 3 , and Supplementary Tables 7 and 8 ).
|
[
{
"end": 207,
"label": "Tissue",
"start": 201,
"text": "tissue"
}
] |
Single_Cell
|
Source paper: PMC12396968
Myeloid cells from all tissues exhibited transcriptional profiles not expressed by other immune lineages (clusters C1–C4), which also varied by tissue (Fig. 3b ).
|
[
{
"end": 41,
"label": "CellType",
"start": 28,
"text": "Myeloid cells"
},
{
"end": 58,
"label": "Tissue",
"start": 51,
"text": "tissues"
},
{
"end": 132,
"label": "CellType",
"start": 117,
"text": "immune lineages"
},
{
"end": 178,
"label": "Tissue",
"start": 172,
"text": "tissue"
}
] |
Single_Cell
|
C1 (chemokine, complement, lipid transport) and C2 (PPAR signaling associated with alveolar macrophages ) were enriched in the JEJ and lung, respectively, particularly in macrophages (Fig. 3c,d ).
|
[
{
"end": 182,
"label": "CellType",
"start": 171,
"text": "macrophages"
},
{
"end": 139,
"label": "Tissue",
"start": 135,
"text": "lung"
},
{
"end": 103,
"label": "CellType",
"start": 83,
"text": "alveolar macrophages"
},
{
"end": 130,
"label": "Tissue",
"start": 127,
"text": "JEJ"
}
] |
Single_Cell
|
By contrast, C4 (anti-microbial peptide production and cell signaling) enrichment was explained by increased frequencies of BM and spleen monocytes relative to macrophages rather than transcriptional changes within and across subsets (Extended Data Fig. 3a,b ).
|
[
{
"end": 171,
"label": "CellType",
"start": 160,
"text": "macrophages"
},
{
"end": 126,
"label": "CellType",
"start": 124,
"text": "BM"
},
{
"end": 147,
"label": "CellType",
"start": 131,
"text": "spleen monocytes"
}
] |
Single_Cell
|
Source paper: PMC12396968
Tissue-associated genes within clusters C5–C9 were expressed primarily by T cells and innate lymphocytes (Fig. 3b ).
|
[
{
"end": 109,
"label": "CellType",
"start": 102,
"text": "T cells"
},
{
"end": 132,
"label": "CellType",
"start": 114,
"text": "innate lymphocytes"
}
] |
Single_Cell
|
C5 genes encoding stem-like transcription factors and markers ( TCF7 , LEF1 , ITGA6 ) and LN homing receptors ( CCR7 , SELL ) were enriched in CD4 and CD8 T RM cells and T EM cells in LN (Fig. 3e,f ).
|
[
{
"end": 146,
"label": "CellType",
"start": 143,
"text": "CD4"
},
{
"end": 165,
"label": "CellType",
"start": 151,
"text": "CD8 T RM cells"
},
{
"end": 180,
"label": "CellType",
"start": 170,
"text": "T EM cells"
},
{
"end": 186,
"label": "Tissue",
"start": 184,
"text": "LN"
}
] |
Single_Cell
|
Conversely, C6 genes encoding molecules for mucosal residency ( ITGA1 , CXCR6 , ITGAE ) and gut homing ( CCR9 ) were enriched in CD4 and CD8 T RM cells, γδ T cells, MAIT cells and NK cells in the JEJ (Fig. 3e,f ).
|
[
{
"end": 132,
"label": "CellType",
"start": 129,
"text": "CD4"
},
{
"end": 151,
"label": "CellType",
"start": 137,
"text": "CD8 T RM cells"
},
{
"end": 163,
"label": "CellType",
"start": 153,
"text": "γδ T cells"
},
{
"end": 175,
"label": "CellType",
"start": 165,
"text": "MAIT cells"
},
{
"end": 188,
"label": "CellType",
"start": 180,
"text": "NK cells"
},
{
"end": 199,
"label": "Tissue",
"start": 196,
"text": "JEJ"
}
] |
Single_Cell
|
CD8 T EMRA cells, γδ cells, MAIT cells and NK/ILCs in the JEJ showed reduced expression of C9 genes associated with cytolytic effector function ( GZMB , PRF1 , IFNG , NKG 7) compared to other sites, while C9 was enriched in the lung (Fig. 3b and Extended Data Fig. 3c,d ).
|
[
{
"end": 232,
"label": "Tissue",
"start": 228,
"text": "lung"
},
{
"end": 16,
"label": "CellType",
"start": 0,
"text": "CD8 T EMRA cells"
},
{
"end": 26,
"label": "CellType",
"start": 18,
"text": "γδ cells"
},
{
"end": 38,
"label": "CellType",
"start": 28,
"text": "MAIT cells"
},
{
"end": 50,
"label": "CellType",
"start": 43,
"text": "NK/ILCs"
},
{
"end": 61,
"label": "Tissue",
"start": 58,
"text": "JEJ"
}
] |
Single_Cell
|
C7 genes associated with protein metabolism were enriched in NK/ILCs and innate T cells in the JEJ, while C8 genes encoding chemokines ( CCL4 , XCL1 ) and innate lymphocyte functions ( KLRC1 , NCR1 ) were expressed by T cell and NK/ILC subsets across all sites (Fig. 3b and Extended Data Fig. 3e,f ).
|
[
{
"end": 224,
"label": "CellType",
"start": 218,
"text": "T cell"
},
{
"end": 68,
"label": "CellType",
"start": 61,
"text": "NK/ILCs"
},
{
"end": 87,
"label": "CellType",
"start": 73,
"text": "innate T cells"
},
{
"end": 98,
"label": "Tissue",
"start": 95,
"text": "JEJ"
},
{
"end": 243,
"label": "CellType",
"start": 229,
"text": "NK/ILC subsets"
}
] |
Single_Cell
|
Therefore, this analysis identified shared gene expression profiles across T and innate lymphocyte subsets that varied by site.
|
[
{
"end": 76,
"label": "CellType",
"start": 75,
"text": "T"
},
{
"end": 106,
"label": "CellType",
"start": 81,
"text": "innate lymphocyte subsets"
}
] |
Single_Cell
|
Source paper: PMC12396968
Tissue-enriched signatures for B cells (C10–C13) were mostly associated with specific subsets (Fig. 3b,g,h and Extended Data Fig. 3g,h ).
|
[
{
"end": 66,
"label": "CellType",
"start": 59,
"text": "B cells"
}
] |
Single_Cell
|
C10 included cell cycle genes and was enriched in B cells and plasma cells in the lungs (Fig. 3g,h ), possibly because of higher plasmablast abundance.
|
[
{
"end": 57,
"label": "CellType",
"start": 50,
"text": "B cells"
},
{
"end": 87,
"label": "Tissue",
"start": 82,
"text": "lungs"
},
{
"end": 74,
"label": "CellType",
"start": 62,
"text": "plasma cells"
},
{
"end": 140,
"label": "CellType",
"start": 129,
"text": "plasmablast"
}
] |
Single_Cell
|
JEJ B cells showed increased expression of C12 (B cell differentiation and protein transport) and C13 (B cell activation) genes (Fig. 3b ), which were derived from plasma cells comprising the majority of the B cell lineage in intestinal sites (Fig. 3g,h ).
|
[
{
"end": 11,
"label": "CellType",
"start": 0,
"text": "JEJ B cells"
},
{
"end": 176,
"label": "CellType",
"start": 164,
"text": "plasma cells"
},
{
"end": 222,
"label": "CellType",
"start": 208,
"text": "B cell lineage"
},
{
"end": 242,
"label": "Tissue",
"start": 226,
"text": "intestinal sites"
}
] |
Single_Cell
|
Source paper: PMC12396968
We also applied consensus single-cell hierarchical Poisson factorization (scHPF) to identify gene co-expression patterns common to different immune lineages or sites (considering the JEJ, lung and LN) (Extended Data Fig. 4a and Supplementary Table 9 ).
|
[
{
"end": 220,
"label": "Tissue",
"start": 216,
"text": "lung"
},
{
"end": 227,
"label": "Tissue",
"start": 225,
"text": "LN"
},
{
"end": 214,
"label": "Tissue",
"start": 211,
"text": "JEJ"
},
{
"end": 184,
"label": "CellType",
"start": 169,
"text": "immune lineages"
}
] |
Single_Cell
|
We found a proliferation module enriched in the lungs, a lymphoid-specific module in the LNs, an intestine-specific residency module and modules associated with effector and cytolytic functions prominent in the lungs but not JEJ or LNs (Extended Data Fig. 4a–d ).
|
[
{
"end": 53,
"label": "Tissue",
"start": 48,
"text": "lungs"
},
{
"end": 216,
"label": "Tissue",
"start": 211,
"text": "lungs"
},
{
"end": 92,
"label": "Tissue",
"start": 89,
"text": "LNs"
},
{
"end": 228,
"label": "Tissue",
"start": 225,
"text": "JEJ"
},
{
"end": 235,
"label": "Tissue",
"start": 232,
"text": "LNs"
}
] |
Single_Cell
|
The lymphoid module included genes associated with stemness ( KLF7 , LEF1 , SOX4 ) and lymphoid homing ( CCR7 , SELL , ITGA6 ) markers expressed mostly in T cells, some NK cells and ILCs, and not in B cells or myeloid cells (Extended Data Fig. 4b–e and Supplementary Table 10 ).
|
[
{
"end": 206,
"label": "CellType",
"start": 199,
"text": "B cells"
},
{
"end": 162,
"label": "CellType",
"start": 155,
"text": "T cells"
},
{
"end": 177,
"label": "CellType",
"start": 169,
"text": "NK cells"
},
{
"end": 186,
"label": "CellType",
"start": 182,
"text": "ILCs"
},
{
"end": 223,
"label": "CellType",
"start": 210,
"text": "myeloid cells"
}
] |
Single_Cell
|
The JEJ residency module included intestinal tissue residency genes ( CCR9 , ITGAE , CD101 , CD160 ) enriched in T cells, NK cells and ILCs (Extended Data Fig. 4f–h ).
|
[
{
"end": 120,
"label": "CellType",
"start": 113,
"text": "T cells"
},
{
"end": 130,
"label": "CellType",
"start": 122,
"text": "NK cells"
},
{
"end": 139,
"label": "CellType",
"start": 135,
"text": "ILCs"
}
] |
Single_Cell
|
These signatures were also reflected at the surface protein level (Extended Data Fig. 4e,i and Supplementary Table 11 ).
|
[] |
Single_Cell
|
Thus, tissue-specific gene expression modules spanned multiple cell types, suggesting shared tissue adaptations.
|
[] |
Single_Cell
|
Source paper: PMC12396968
The tissue environment poses unique requirements for resident immune populations such as T RM cells, plasma cells and macrophages for maintaining homeostasis .
|
[
{
"end": 157,
"label": "CellType",
"start": 146,
"text": "macrophages"
},
{
"end": 127,
"label": "CellType",
"start": 117,
"text": "T RM cells"
},
{
"end": 141,
"label": "CellType",
"start": 129,
"text": "plasma cells"
},
{
"end": 50,
"label": "Tissue",
"start": 32,
"text": "tissue environment"
},
{
"end": 108,
"label": "CellType",
"start": 81,
"text": "resident immune populations"
}
] |
Single_Cell
|
We integrated the DE analysis shown in Fig. 3 with surface protein expression to define site-specific signatures for resident immune cells (Fig. 4 and Supplementary Table 12 ).
|
[
{
"end": 138,
"label": "CellType",
"start": 117,
"text": "resident immune cells"
}
] |
Single_Cell
|
CD4 and CD8 T RM cells expressed genes and/or surface proteins for tissue residency (CD103, CD101, CD49a), gut homing and localization ( CCR9 , CCR5 for CD4 T RM cells) and reduced PD-1 (for CD8 T RM cells) in intestines relative to lungs and lymphoid organs (Fig. 4a–f ).
|
[
{
"end": 220,
"label": "Tissue",
"start": 210,
"text": "intestines"
},
{
"end": 238,
"label": "Tissue",
"start": 233,
"text": "lungs"
},
{
"end": 3,
"label": "CellType",
"start": 0,
"text": "CD4"
},
{
"end": 22,
"label": "CellType",
"start": 8,
"text": "CD8 T RM cells"
},
{
"end": 167,
"label": "CellType",
"start": 153,
"text": "CD4 T RM cells"
},
{
"end": 205,
"label": "CellType",
"start": 191,
"text": "CD8 T RM cells"
},
{
"end": 258,
"label": "Tissue",
"start": 243,
"text": "lymphoid organs"
}
] |
Single_Cell
|
Lung T RM cells showed increased expression of effector or cytotoxicity ( IFNG , GZMH , GZMA , PRF1 ) and regulatory ( CTLA4 ) genes relative to the JEJ and lymphoid organs; T RM cells in LN, spleen and BM had higher expression of stem-like markers ( TCF7 , KLF2 ) and certain integrins and costimulatory markers ( ITGB2 , CD27, CD28, ICOS) relative to the JEJ and lungs (Fig. 4a–f ).
|
[
{
"end": 370,
"label": "Tissue",
"start": 365,
"text": "lungs"
},
{
"end": 198,
"label": "Tissue",
"start": 192,
"text": "spleen"
},
{
"end": 15,
"label": "CellType",
"start": 0,
"text": "Lung T RM cells"
},
{
"end": 152,
"label": "Tissue",
"start": 149,
"text": "JEJ"
},
{
"end": 172,
"label": "Tissue",
"start": 157,
"text": "lymphoid organs"
},
{
"end": 184,
"label": "CellType",
"start": 174,
"text": "T RM cells"
},
{
"end": 190,
"label": "Tissue",
"start": 188,
"text": "LN"
},
{
"end": 205,
"label": "Tissue",
"start": 203,
"text": "BM"
},
{
"end": 360,
"label": "Tissue",
"start": 357,
"text": "JEJ"
}
] |
Single_Cell
|
These site-specific profiles for T RM cells showed adaptations related to migration, localization and function.
|
[
{
"end": 43,
"label": "CellType",
"start": 33,
"text": "T RM cells"
}
] |
Single_Cell
|
Source paper: PMC12396968
Tissue plasma cells and macrophages also exhibited distinct tissue signatures.
|
[
{
"end": 63,
"label": "CellType",
"start": 52,
"text": "macrophages"
},
{
"end": 47,
"label": "CellType",
"start": 28,
"text": "Tissue plasma cells"
}
] |
Single_Cell
|
For plasma cells, we found several JEJ-enriched genes, including IGHA2 (consistent with predominant IgA plasma cells in the gut), the non-classical HLA molecule CD1d, plasma cell transcription factors ( RUNX2 , ID3 ) and the tissue residency marker CD69 (Fig. 4g–i ).
|
[
{
"end": 127,
"label": "Tissue",
"start": 124,
"text": "gut"
},
{
"end": 16,
"label": "CellType",
"start": 4,
"text": "plasma cells"
},
{
"end": 116,
"label": "CellType",
"start": 100,
"text": "IgA plasma cells"
}
] |
Single_Cell
|
Plasma cells in lungs, and to a lesser extent, LN and spleen, expressed higher levels of integrins (CD11c, CD18) (Fig. 4g–i ).
|
[
{
"end": 21,
"label": "Tissue",
"start": 16,
"text": "lungs"
},
{
"end": 60,
"label": "Tissue",
"start": 54,
"text": "spleen"
},
{
"end": 12,
"label": "CellType",
"start": 0,
"text": "Plasma cells"
},
{
"end": 49,
"label": "Tissue",
"start": 47,
"text": "LN"
}
] |
Single_Cell
|
JEJ macrophages had increased expression of integrins ( ICAM1 , ITGA4 ), chemokines ( CCL24 , CCL3L1 ) and regulators of macrophage activation (for example, SLAMF7 ) , whereas lung macrophages had higher expression of CD11c ( ITGAX ), markers of efferocytosis ( MRC1 , MARCO ) and lipid metabolism ( PPARG , TREM2 , FABP4 ) (Fig. 4j–l ), consistent with alveolar macrophages .
|
[
{
"end": 374,
"label": "CellType",
"start": 354,
"text": "alveolar macrophages"
},
{
"end": 15,
"label": "CellType",
"start": 0,
"text": "JEJ macrophages"
},
{
"end": 192,
"label": "CellType",
"start": 176,
"text": "lung macrophages"
}
] |
Single_Cell
|
Lastly, macrophages in the spleen expressed markers of red pulp macrophages ( SPIC , VCAM1 ) (Fig. 4j ).
|
[
{
"end": 19,
"label": "CellType",
"start": 8,
"text": "macrophages"
},
{
"end": 33,
"label": "Tissue",
"start": 27,
"text": "spleen"
},
{
"end": 75,
"label": "CellType",
"start": 55,
"text": "red pulp macrophages"
}
] |
Single_Cell
|
These observations revealed site-specific signatures for activation, migration, metabolism and cell–cell interactions involved in tissue residency.
|
[] |
Single_Cell
|
Source paper: PMC12396968
We investigated age-associated effects across immune lineages and tissues.
|
[
{
"end": 89,
"label": "CellType",
"start": 74,
"text": "immune lineages"
},
{
"end": 101,
"label": "Tissue",
"start": 94,
"text": "tissues"
}
] |
Single_Cell
|
A global analysis of transcriptional variance within each major lineage revealed that tissue site explained the majority of variance, while age accounted for a much smaller fraction (Fig. 5a and Supplementary Table 13 ).
|
[
{
"end": 71,
"label": "CellType",
"start": 58,
"text": "major lineage"
},
{
"end": 97,
"label": "Tissue",
"start": 86,
"text": "tissue site"
}
] |
Single_Cell
|
Most of the top age-dependent genes in each lineage (Fig. 5b ) also exhibited tissue-specific variation.
|
[
{
"end": 51,
"label": "CellType",
"start": 44,
"text": "lineage"
}
] |
Single_Cell
|
Immune cell composition in the different sites was largely maintained across age, except for significantly decreased frequencies of CD8 T N cells in the blood and LNs, concomitant increases in T EM cells in the blood and T RM cells in the LNs and lower frequencies of classical monocytes in the BM (Fig. 5c and Supplementary Table 14 ).
|
[
{
"end": 158,
"label": "Tissue",
"start": 153,
"text": "blood"
},
{
"end": 216,
"label": "Tissue",
"start": 211,
"text": "blood"
},
{
"end": 145,
"label": "CellType",
"start": 132,
"text": "CD8 T N cells"
},
{
"end": 166,
"label": "Tissue",
"start": 163,
"text": "LNs"
},
{
"end": 203,
"label": "CellType",
"start": 193,
"text": "T EM cells"
},
{
"end": 231,
"label": "CellType",
"start": 221,
"text": "T RM cells"
},
{
"end": 242,
"label": "Tissue",
"start": 239,
"text": "LNs"
},
{
"end": 287,
"label": "CellType",
"start": 268,
"text": "classical monocytes"
},
{
"end": 297,
"label": "Tissue",
"start": 295,
"text": "BM"
}
] |
Single_Cell
|
These results indicate that tissue-driven immune cell composition and profile are largely maintained with age.
|
[] |
Single_Cell
|
Source paper: PMC12396968
To interrogate specific effects of aging on immune cells across lineages and sites, we conducted a separate DE analysis for each tissue group and immune subset with sufficient representation, comparing younger (<40 years) versus older (>40 years) individuals, while controlling for sex, CMV status and other covariates (Supplementary Tables 15 – 17 ).
|
[
{
"end": 84,
"label": "CellType",
"start": 72,
"text": "immune cells"
},
{
"end": 100,
"label": "CellType",
"start": 92,
"text": "lineages"
},
{
"end": 110,
"label": "Tissue",
"start": 105,
"text": "sites"
}
] |
Single_Cell
|
An embedding of similarities between age-related DEGs revealed that some immune cells exhibited changes specific to tissue site (for example, T cells in the LN, lymphocytes in the JEJ), while others showed subset-specific changes independent of site (for example, monocytes in blood, BM and lung, and memory B cells in LNs and lung) (Fig. 5d ).
|
[
{
"end": 172,
"label": "CellType",
"start": 161,
"text": "lymphocytes"
},
{
"end": 273,
"label": "CellType",
"start": 264,
"text": "monocytes"
},
{
"end": 149,
"label": "CellType",
"start": 142,
"text": "T cells"
},
{
"end": 282,
"label": "Tissue",
"start": 277,
"text": "blood"
},
{
"end": 295,
"label": "Tissue",
"start": 291,
"text": "lung"
},
{
"end": 331,
"label": "Tissue",
"start": 327,
"text": "lung"
},
{
"end": 85,
"label": "CellType",
"start": 73,
"text": "immune cells"
},
{
"end": 127,
"label": "Tissue",
"start": 116,
"text": "tissue site"
},
{
"end": 159,
"label": "Tissue",
"start": 157,
"text": "LN"
},
{
"end": 183,
"label": "Tissue",
"start": 180,
"text": "JEJ"
},
{
"end": 286,
"label": "Tissue",
"start": 284,
"text": "BM"
},
{
"end": 315,
"label": "CellType",
"start": 301,
"text": "memory B cells"
},
{
"end": 322,
"label": "Tissue",
"start": 319,
"text": "LNs"
}
] |
Single_Cell
|
Source paper: PMC12396968
We identified genes regulated with age in each subset and tissue by integrating DE results with GSEA (Supplementary Fig. 8a ).
|
[
{
"end": 92,
"label": "Tissue",
"start": 86,
"text": "tissue"
}
] |
Single_Cell
|
For myeloid lineage cells, mucosal sites had the most age-related DEGs, with similar trends in lymphoid organs (Fig. 5e–g ).
|
[
{
"end": 25,
"label": "CellType",
"start": 4,
"text": "myeloid lineage cells"
},
{
"end": 40,
"label": "Tissue",
"start": 27,
"text": "mucosal sites"
},
{
"end": 110,
"label": "Tissue",
"start": 95,
"text": "lymphoid organs"
}
] |
Single_Cell
|
Age-related changes in classical monocytes included increased expression of genes associated with proliferation and inflammation ( KRAS , CALM1 ) and decreased expression of genes for macrophage differentiation (for example, RAB44 ) (Fig. 5e ); non-classical monocytes showed age-associated increase in expression of genes for cell–cell interactions ( LGALS1 , ITGA9 ) and decreased expression of metabolism and mitochondrial regulation genes ( LYRM7 , SARS2 ) (Fig. 5f ).
|
[
{
"end": 42,
"label": "CellType",
"start": 23,
"text": "classical monocytes"
},
{
"end": 268,
"label": "CellType",
"start": 245,
"text": "non-classical monocytes"
}
] |
Single_Cell
|
Macrophages had decreased expression of genes associated with metabolism and mitochondrial fitness ( MARC1 , MTOR ) and increased expression of genes associated with M2 macrophages ( ID1 , ADGRE1 NPR2 ) and interferon signaling ( MX2 ) (Fig. 5g ) along with increased CD95 (Fas) at the protein level (Fig. 5h ).
|
[
{
"end": 11,
"label": "CellType",
"start": 0,
"text": "Macrophages"
},
{
"end": 180,
"label": "CellType",
"start": 166,
"text": "M2 macrophages"
}
] |
Single_Cell
|
Together, these age-related changes in monocytes and macrophages were subset-specific, enriched in mucosal sites and indicated decreased overall fitness.
|
[
{
"end": 64,
"label": "CellType",
"start": 53,
"text": "macrophages"
},
{
"end": 48,
"label": "CellType",
"start": 39,
"text": "monocytes"
},
{
"end": 112,
"label": "Tissue",
"start": 99,
"text": "mucosal sites"
}
] |
Single_Cell
|
Source paper: PMC12396968
We used scHPF to identify age-associated gene signatures for myeloid cells and GSEA to assess their expression in different subsets and sites (Supplementary Tables 18 and 19 ).
|
[
{
"end": 102,
"label": "CellType",
"start": 89,
"text": "myeloid cells"
}
] |
Single_Cell
|
We uncovered an APOE–TREM2 signature, including apolipoprotein genes ( APOC1 , APOC2 and APOE ) and TREM2 , a triggering receptor expressed on myeloid cells that binds ApoE and facilitates macrophage functions, such as phagocytosis and chemotaxis, and induces metabolic changes (Fig. 5i ).
|
[
{
"end": 156,
"label": "CellType",
"start": 143,
"text": "myeloid cells"
}
] |
Single_Cell
|
This APOE–TREM2 signature was significantly downregulated with age in monocytes and macrophages in the lungs, lymphoid organs and blood (Fig. 5j ), and in an independent published dataset from human lungs ( n = 29; see Methods ) (Fig. 5k ).
|
[
{
"end": 95,
"label": "CellType",
"start": 84,
"text": "macrophages"
},
{
"end": 79,
"label": "CellType",
"start": 70,
"text": "monocytes"
},
{
"end": 135,
"label": "Tissue",
"start": 130,
"text": "blood"
},
{
"end": 108,
"label": "Tissue",
"start": 103,
"text": "lungs"
},
{
"end": 125,
"label": "Tissue",
"start": 110,
"text": "lymphoid organs"
},
{
"end": 204,
"label": "Tissue",
"start": 193,
"text": "human lungs"
}
] |
Single_Cell
|
Overall, this analysis showed subset and site-specific features of macrophage aging involving a major functional and metabolic pathway.
|
[] |
Single_Cell
|
Source paper: PMC12396968
We applied the above approaches to identify age-associated signatures in T cells and B cells.
|
[
{
"end": 120,
"label": "CellType",
"start": 113,
"text": "B cells"
},
{
"end": 108,
"label": "CellType",
"start": 101,
"text": "T cells"
}
] |
Single_Cell
|
For CD4 T cells, CD8 T cells and B cells, there were relatively few genes (for example, those associated with oxidation and inflammation: SOD1 , IL18BP , IL15 ) that changed over age in two or more subsets within each lineage (Extended Data Fig. 5a–d ).
|
[
{
"end": 40,
"label": "CellType",
"start": 33,
"text": "B cells"
},
{
"end": 15,
"label": "CellType",
"start": 4,
"text": "CD4 T cells"
},
{
"end": 28,
"label": "CellType",
"start": 17,
"text": "CD8 T cells"
}
] |
Single_Cell
|
Pathway analysis revealed increased inflammation, apoptosis and reduced TCR signaling across multiple T cell subsets with age (Supplementary Fig. 8b ).
|
[
{
"end": 116,
"label": "CellType",
"start": 102,
"text": "T cell subsets"
}
] |
Single_Cell
|
Despite the paucity of age-associated gene expression changes across subsets, CD8 T EMRA cells exhibited multiple age-associated changes conserved across sites; these included increased expression of NK cell genes ( NCAM1 , KLRF1 , GNLY ) and the NK cell marker CD56, consistent with findings in blood , and reduced expression of genes associated with signaling ( CD6 , JAK3 ), proliferation and metabolism ( TCF7 , RPTOR ) (Fig. 6a,b ).
|
[
{
"end": 301,
"label": "Tissue",
"start": 296,
"text": "blood"
}
] |
Single_Cell
|
Source paper: PMC12396968
By scHPF analysis, we identified two prominent age-associated transcriptional signatures shared across multiple CD8 T cell subsets.
|
[
{
"end": 158,
"label": "CellType",
"start": 140,
"text": "CD8 T cell subsets"
}
] |
Single_Cell
|
A cytokine signature, containing genes for effector cytokines and chemokines (for example, CCL3 , CCL4 , XCL1 , IFNG , TNF ), was increased with age in all CD8 T cell subsets and γδ T cells across all sites examined (Fig. 6c,d ).
|
[
{
"end": 174,
"label": "CellType",
"start": 156,
"text": "CD8 T cell subsets"
},
{
"end": 189,
"label": "CellType",
"start": 179,
"text": "γδ T cells"
}
] |
Single_Cell
|
This aging signature was also detected in published datasets from human lungs (Fig. 6e ) and in peripheral blood mononuclear cells (PBMCs) from the Sound Life cohort ( n = 96, age 26–65 years) within the Human Immune Health Atlas (Extended Data Fig. 5e ).
|
[
{
"end": 137,
"label": "CellType",
"start": 132,
"text": "PBMCs"
},
{
"end": 130,
"label": "CellType",
"start": 96,
"text": "peripheral blood mononuclear cells"
},
{
"end": 77,
"label": "Tissue",
"start": 66,
"text": "human lungs"
}
] |
Single_Cell
|
A second signature contained GZMK encoding the cytolytic molecule granzyme K, the transcription factor EOMES and activation or signaling markers ( PDCD1 , HLA-DR , FCRL3 ) (Fig. 6f ).
|
[] |
Single_Cell
|
This signature aligned with a granzyme K-containing, age-associated signature identified in T cells in aged mice and human blood and in PBMCs from the Human Immune Health Atlas (Extended Data Fig. 5f ).
|
[
{
"end": 141,
"label": "CellType",
"start": 136,
"text": "PBMCs"
},
{
"end": 99,
"label": "CellType",
"start": 92,
"text": "T cells"
},
{
"end": 128,
"label": "Tissue",
"start": 117,
"text": "human blood"
}
] |
Single_Cell
|
This GZMK signature was increased with age in CD8 T EMRA cells, γδ T cells and CD8 T EM cells across tissues but not in CD8 T RM cells in lungs and JEJ (Fig. 6g ).
|
[
{
"end": 143,
"label": "Tissue",
"start": 138,
"text": "lungs"
},
{
"end": 62,
"label": "CellType",
"start": 46,
"text": "CD8 T EMRA cells"
},
{
"end": 74,
"label": "CellType",
"start": 64,
"text": "γδ T cells"
},
{
"end": 93,
"label": "CellType",
"start": 79,
"text": "CD8 T EM cells"
},
{
"end": 108,
"label": "Tissue",
"start": 101,
"text": "tissues"
},
{
"end": 134,
"label": "CellType",
"start": 120,
"text": "CD8 T RM cells"
},
{
"end": 151,
"label": "Tissue",
"start": 148,
"text": "JEJ"
}
] |
Single_Cell
|
The frequency and clonal expansion of CD8 T EMRA cells enriched in the GZMK signature was higher in older than in younger donors (Fig. 6h,i ).
|
[
{
"end": 54,
"label": "CellType",
"start": 38,
"text": "CD8 T EMRA cells"
}
] |
Single_Cell
|
These results show distinct age-associated signatures in mucosal resident T cells compared to circulation.
|
[
{
"end": 81,
"label": "CellType",
"start": 57,
"text": "mucosal resident T cells"
},
{
"end": 105,
"label": "CellType",
"start": 94,
"text": "circulation"
}
] |
Single_Cell
|
Source paper: PMC12396968
For B cells, there were more age-related DEGs in memory compared to naive B cells in LNs (Fig. 6j and Extended Data Fig. 5d ).
|
[
{
"end": 39,
"label": "CellType",
"start": 32,
"text": "B cells"
},
{
"end": 109,
"label": "CellType",
"start": 96,
"text": "naive B cells"
},
{
"end": 116,
"label": "Tissue",
"start": 113,
"text": "LNs"
}
] |
Single_Cell
|
Memory B cells from older donors had increased expression of genes associated with inflammatory cytokines ( IL18 , IL18BP ), cell adhesion ( CD58 , LGALS1 ) and cell death or autophagy ( FAS , ITM2A ), along with reduced expression of proliferation ( CDCA7 , IL2RA ), lipid metabolism ( ACSM3 , PNPLA7 ) and differentiation markers (Fig. 6j ).
|
[
{
"end": 14,
"label": "CellType",
"start": 0,
"text": "Memory B cells"
}
] |
Single_Cell
|
Select IL-18 pathway-associated genes in B cells and CD4 T cells in blood were validated in the Human Immune Health Atlas cohort (Supplementary Fig. 9a,b ).
|
[
{
"end": 48,
"label": "CellType",
"start": 41,
"text": "B cells"
},
{
"end": 73,
"label": "Tissue",
"start": 68,
"text": "blood"
},
{
"end": 64,
"label": "CellType",
"start": 53,
"text": "CD4 T cells"
}
] |
Single_Cell
|
Transcript and/or surface expression of IgM ( IGHM ) and IGHD were reduced in older compared to younger B cells, and the frequency of IgM B cells decreased with age (Fig. 6k,l and Supplementary Table 20 ).
|
[
{
"end": 83,
"label": "CellType",
"start": 78,
"text": "older"
},
{
"end": 111,
"label": "CellType",
"start": 96,
"text": "younger B cells"
},
{
"end": 145,
"label": "CellType",
"start": 134,
"text": "IgM B cells"
}
] |
Single_Cell
|
We identified by scHPF that a gene signature related to RAS signaling ( RASA4B , RASGRF1 , GAB2 ) downstream of the BCR was downregulated with age in naive and memory B cells across all sites (Fig. 6m,n ).
|
[
{
"end": 174,
"label": "CellType",
"start": 160,
"text": "memory B cells"
},
{
"end": 155,
"label": "CellType",
"start": 150,
"text": "naive"
}
] |
Single_Cell
|
We validated this age-associated signature in BM-derived B cells from an independent dataset ( n = 39, age 2–84 years) and in PBMCs from the Human Immune Health Atlas (Fig. 6o and Extended Data Fig. 5g ).
|
[
{
"end": 131,
"label": "CellType",
"start": 126,
"text": "PBMCs"
},
{
"end": 64,
"label": "CellType",
"start": 46,
"text": "BM-derived B cells"
}
] |
Single_Cell
|
Pathway analysis further revealed increased inflammation and reduced BCR signaling in LN B cells with age (Supplementary Fig. 8c ).
|
[
{
"end": 96,
"label": "CellType",
"start": 86,
"text": "LN B cells"
}
] |
Single_Cell
|
These results showed that B cells exhibited diminished signaling and functional dysregulation across tissues over age.
|
[
{
"end": 33,
"label": "CellType",
"start": 26,
"text": "B cells"
},
{
"end": 108,
"label": "Tissue",
"start": 101,
"text": "tissues"
}
] |
Single_Cell
|
Source paper: PMC12396968
CMV infection drives immune cell alterations, including increased accumulation of T EMRA cells with age in blood, spleen and lungs .
|
[
{
"end": 140,
"label": "Tissue",
"start": 135,
"text": "blood"
},
{
"end": 158,
"label": "Tissue",
"start": 153,
"text": "lungs"
},
{
"end": 148,
"label": "Tissue",
"start": 142,
"text": "spleen"
},
{
"end": 122,
"label": "CellType",
"start": 110,
"text": "T EMRA cells"
}
] |
Single_Cell
|
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