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Moreover, gene set analysis of these 329 genes showed, although non-significant in this limited set of genes, alterations in processes related to cell surface, cell adhesion and epithelial to mesenchymal transition (Supplementary Fig. S6).
|
[] |
ChemBL_V1
|
The growth morphology of bioproduction cell lines is of great importance for culture maintenance and efficiency of industrial bioprocessing.
|
[] |
ChemBL_V1
|
In order to look into gene expression variations correlating with adherent and suspension HEK 293 cell lines, differential expression analysis between adherent and suspension HEK293 progeny cell lines was performed.
|
[
{
"end": 97,
"label": "CellLine",
"start": 90,
"text": "HEK 293"
},
{
"end": 181,
"label": "CellLine",
"start": 175,
"text": "HEK293"
}
] |
ChemBL_V1
|
As results from the overall comparison of transcriptomic profiles of the HEK293 cell lines showed that the parental HEK293 cell line is highly differentiated from all of the progeny cell lines and moreover, that the Freestyle 293-F cell line is very similar to the 293-F cell line, HEK293 and Freestyle 293-F were excluded from this analysis, so as not to skew the data.
|
[
{
"end": 79,
"label": "CellLine",
"start": 73,
"text": "HEK293"
},
{
"end": 122,
"label": "CellLine",
"start": 116,
"text": "HEK293"
},
{
"end": 288,
"label": "CellLine",
"start": 282,
"text": "HEK293"
}
] |
ChemBL_V1
|
Enrichment analysis of the differentially expressed genes between adherent (293T and 293E) and suspension (293-H and 293-F) progeny cell lines showed significant expression differences of similar gene sets as in the comparison between progeny cell lines and the parental HEK293 (Figs. 3a, 4a, Supplementary Table S6).
|
[
{
"end": 80,
"label": "CellLine",
"start": 76,
"text": "293T"
},
{
"end": 89,
"label": "CellLine",
"start": 85,
"text": "293E"
},
{
"end": 112,
"label": "CellLine",
"start": 107,
"text": "293-H"
},
{
"end": 122,
"label": "CellLine",
"start": 117,
"text": "293-F"
},
{
"end": 277,
"label": "CellLine",
"start": 271,
"text": "HEK293"
}
] |
ChemBL_V1
|
For instance, the suspension progeny cell lines had a significant up-regulation of gene sets involved in cellular compartment organization such as cell morphogenesis, cell junction-, cell membrane- and cytoskeleton organization.
|
[] |
ChemBL_V1
|
Interestingly, there is no significant change in the expression of the extracellular matrix organization gene set between suspension and adherent HEK293 progeny cell lines.
|
[
{
"end": 152,
"label": "CellLine",
"start": 146,
"text": "HEK293"
}
] |
ChemBL_V1
|
Perhaps as expected, there was significant differential expression observed for the cell adhesion, cell differentiation, cell morphogenesis and cell motility gene sets.
|
[] |
ChemBL_V1
|
All of the above-mentioned gene sets, including cell adhesion, were up-regulated in suspension HEK293 cells as compared to adherent.
|
[
{
"end": 101,
"label": "CellLine",
"start": 95,
"text": "HEK293"
}
] |
ChemBL_V1
|
When looking at the most significantly differentially expressed genes (adjusted p-value < 0.01) amongst the cell adhesion gene set, many genes of the cadherin superfamily of cell adhesion molecules were found up-regulated in suspension cell lines compared to adherent HEK293 progeny cells (Supplementary Table S7).Figure 4Gene set analysis identified biological process and metabolic changes between suspension and adherent HEK293 progeny cell lineages. (
|
[
{
"end": 274,
"label": "CellLine",
"start": 268,
"text": "HEK293"
},
{
"end": 430,
"label": "CellLine",
"start": 424,
"text": "HEK293"
}
] |
ChemBL_V1
|
Heatmap of gene set analysis using GO biological processes and Piano consensus scores showed a different expression pattern between suspension cells (293-H and 293-F) and adherent cells (293E and 293T).
|
[
{
"end": 155,
"label": "CellLine",
"start": 150,
"text": "293-H"
},
{
"end": 165,
"label": "CellLine",
"start": 160,
"text": "293-F"
},
{
"end": 191,
"label": "CellLine",
"start": 187,
"text": "293E"
},
{
"end": 200,
"label": "CellLine",
"start": 196,
"text": "293T"
}
] |
ChemBL_V1
|
Low consensus scores, represented by a dark blue color, indicate more significant differences. (
|
[] |
ChemBL_V1
|
Metabolic genes set analysis for comparing metabolic differences between suspension and adherent HEK293 progeny cell lines.
|
[
{
"end": 103,
"label": "CellLine",
"start": 97,
"text": "HEK293"
}
] |
ChemBL_V1
|
The size of each node corresponds to the number of genes in each of these pathways, thickness of connections between nodes corresponds to the number shared genes between pathways and the colors of the nodes shows the p-value for the given metabolic process.
|
[] |
ChemBL_V1
|
Gene set analysis identified biological process and metabolic changes between suspension and adherent HEK293 progeny cell lineages. (
|
[
{
"end": 108,
"label": "CellLine",
"start": 102,
"text": "HEK293"
}
] |
ChemBL_V1
|
Heatmap of gene set analysis using GO biological processes and Piano consensus scores showed a different expression pattern between suspension cells (293-H and 293-F) and adherent cells (293E and 293T).
|
[
{
"end": 155,
"label": "CellLine",
"start": 150,
"text": "293-H"
},
{
"end": 165,
"label": "CellLine",
"start": 160,
"text": "293-F"
},
{
"end": 191,
"label": "CellLine",
"start": 187,
"text": "293E"
},
{
"end": 200,
"label": "CellLine",
"start": 196,
"text": "293T"
}
] |
ChemBL_V1
|
Low consensus scores, represented by a dark blue color, indicate more significant differences. (
|
[] |
ChemBL_V1
|
Metabolic genes set analysis for comparing metabolic differences between suspension and adherent HEK293 progeny cell lines.
|
[
{
"end": 103,
"label": "CellLine",
"start": 97,
"text": "HEK293"
}
] |
ChemBL_V1
|
The size of each node corresponds to the number of genes in each of these pathways, thickness of connections between nodes corresponds to the number shared genes between pathways and the colors of the nodes shows the p-value for the given metabolic process.
|
[] |
ChemBL_V1
|
In order to evaluate what metabolic impact the differentially expressed genes may have on cells in suspension compared to the adherent state, a generic human metabolic model, HMR2, was used to generate a set of metabolic genes and their assigned pathways to find metabolic pathways with altered expression between adherent and suspension HEK293 progeny cell lines.
|
[
{
"end": 344,
"label": "CellLine",
"start": 338,
"text": "HEK293"
}
] |
ChemBL_V1
|
As shown in Fig. 4b, pathways related to aromatic amino acids and oxidative phosphorylation were significantly down-regulated in suspension cells compared to adherent and had amongst the highest number of differentially expressed genes.
|
[] |
ChemBL_V1
|
Pathways related to retinol, linoleate and nucleotide metabolism were also significantly down-regulated in suspension cell-lines.
|
[] |
ChemBL_V1
|
On the other hand, biosynthesis and metabolism of cholesterol were found to be most significantly up-regulated amongst metabolic pathways in suspension compared to adherent cells.
|
[] |
ChemBL_V1
|
In addition, pathways related to protein modification and fatty acid metabolism (omega-3/6 fatty acid metabolism, fatty acid desaturation, fatty acid biosynthesis and fatty acid elongation) were up-regulated in suspension compared to adherent HEK293 progeny cell lines.
|
[
{
"end": 249,
"label": "CellLine",
"start": 243,
"text": "HEK293"
}
] |
ChemBL_V1
|
All results from the metabolic gene set analysis are provided in Supplementary Table S8.
|
[] |
ChemBL_V1
|
Focusing on the pairwise comparisons between HEK293 cell lines, 38 differentially expressed genes were identified common to all adherent to suspension pairwise comparisons (red column in Figs. 3b, 5a, Supplementary Table S5).
|
[
{
"end": 51,
"label": "CellLine",
"start": 45,
"text": "HEK293"
}
] |
ChemBL_V1
|
Three of the genes (ARRDC3, HMGCS1 and PCYOX1L) had the same directional gene copy number variation (gain or loss) compared to gene expression fold-changes (up or down) of all suspension compared to adherent cells, which may at least partly explain the differential expression of these genes between the groups.
|
[] |
ChemBL_V1
|
Gene enrichment analysis of this set of 38 differentially expressed genes between adherent and suspension cells, performed using Enrichr, predicted the cholesterol biosynthetic process pathway as the cellular pathway most affected by this expression variation (Fig. 5b).
|
[] |
ChemBL_V1
|
This result further emphasizes the differential expression between adherent and suspension cells of genes involved in the cholesterol pathway, mentioned above.
|
[] |
ChemBL_V1
|
Among the 38 common differentially expressed genes MSMO1, IDI1, NPC1L1, INSIG1 and HMGCS1 are directly related to cholesterol biosynthesis (GO:0006695 and/or GO:0008203, Fig. 5b).
|
[] |
ChemBL_V1
|
Each of these genes had at least a two-fold increase in expression in the suspension cells compared with the adherent cell-lines.
|
[] |
ChemBL_V1
|
Based on these findings, we sought to predict the effect of the differentially expressed genes between adherent and suspension HEK293 cell lines on the cholesterol biosynthesis of the cells using Ingenuity pathway analysis (IPA).
|
[
{
"end": 133,
"label": "CellLine",
"start": 127,
"text": "HEK293"
}
] |
ChemBL_V1
|
Although the MSMO1, IDI1 and HMGCS1 genes were all up-regulated in 293-F and 293-H compared to HEK293, the down-regulation of the lathosterol oxidase gene (SC5D), which gene product is in downstream steps of the pathway, resulted in a predicted reduction in cholesterol production in 293-F and 293-H cells compared to HEK293 (Supplementary Fig. S7).
|
[
{
"end": 72,
"label": "CellLine",
"start": 67,
"text": "293-F"
},
{
"end": 82,
"label": "CellLine",
"start": 77,
"text": "293-H"
},
{
"end": 101,
"label": "CellLine",
"start": 95,
"text": "HEK293"
},
{
"end": 289,
"label": "CellLine",
"start": 284,
"text": "293-F"
},
{
"end": 299,
"label": "CellLine",
"start": 294,
"text": "293-H"
},
{
"end": 324,
"label": "CellLine",
"start": 318,
"text": "HEK293"
}
] |
ChemBL_V1
|
Comparisons between suspension cell lines (293-F and 293-H) and adherent progeny cell lines (293E and 293T) did not result in any predicted changes in cholesterol biosynthesis (data not shown).Figure 5Evaluation of common DE genes between adherent and suspension HEK293 cells identified cholesterol biosynthesis as the main enriched pathway. (
|
[
{
"end": 48,
"label": "CellLine",
"start": 43,
"text": "293-F"
},
{
"end": 58,
"label": "CellLine",
"start": 53,
"text": "293-H"
},
{
"end": 97,
"label": "CellLine",
"start": 93,
"text": "293E"
},
{
"end": 106,
"label": "CellLine",
"start": 102,
"text": "293T"
},
{
"end": 269,
"label": "CellLine",
"start": 263,
"text": "HEK293"
}
] |
ChemBL_V1
|
Heat map with TPM values for each DE gene common to all adherent to suspension comparisons. (
|
[] |
ChemBL_V1
|
The top ten most enriched biological GO terms of the 38 common DE genes between adherent and suspension cells based on gene enrichment analysis.
|
[] |
ChemBL_V1
|
Length and color of bars both show significance of adjusted p-value for the hypergeometric test.
|
[] |
ChemBL_V1
|
Also, genes mentioned in each bar are the genes that belong to enriched GO term and present in the list of 38 DE genes.
|
[] |
ChemBL_V1
|
Evaluation of common DE genes between adherent and suspension HEK293 cells identified cholesterol biosynthesis as the main enriched pathway. (
|
[
{
"end": 68,
"label": "CellLine",
"start": 62,
"text": "HEK293"
}
] |
ChemBL_V1
|
Heat map with TPM values for each DE gene common to all adherent to suspension comparisons. (
|
[] |
ChemBL_V1
|
The top ten most enriched biological GO terms of the 38 common DE genes between adherent and suspension cells based on gene enrichment analysis.
|
[] |
ChemBL_V1
|
Length and color of bars both show significance of adjusted p-value for the hypergeometric test.
|
[] |
ChemBL_V1
|
Also, genes mentioned in each bar are the genes that belong to enriched GO term and present in the list of 38 DE genes.
|
[] |
ChemBL_V1
|
As four out of the 38 differentially expressed genes (LOX, SMAD7, ID1 & TXNIP) have previously been shown to have a role in the epithelial to mesenchymal transition (EMT) pathway, we evaluated the role of this pathway in the transition from adherent to suspension cell growth of these HEK293 cell lines.
|
[
{
"end": 291,
"label": "CellLine",
"start": 285,
"text": "HEK293"
}
] |
ChemBL_V1
|
The normalized expression of a set of EMT markers showed that the parental HEK293 actually had the highest level of expression of various mesenchymal markers (N-cadherin, vimentin and fibronectin) of all the six cell lines (Supplementary Fig. S8).
|
[
{
"end": 81,
"label": "CellLine",
"start": 75,
"text": "HEK293"
}
] |
ChemBL_V1
|
Moreover, when predicting EMT pathway outcomes for suspension cells (293F and 293H) compared to the parental HEK293 strain using IPA, the results predicted reduced EMT in the suspension progeny cells compared to HEK293 (Supplementary Fig. S8).
|
[
{
"end": 73,
"label": "CellLine",
"start": 69,
"text": "293F"
},
{
"end": 82,
"label": "CellLine",
"start": 78,
"text": "293H"
},
{
"end": 115,
"label": "CellLine",
"start": 109,
"text": "HEK293"
},
{
"end": 218,
"label": "CellLine",
"start": 212,
"text": "HEK293"
}
] |
ChemBL_V1
|
However, suspension cells were predicted to have increased disruption of adherence junctions, which is consistent with the suspension cell phenotype.
|
[] |
ChemBL_V1
|
Taken together the comparison between adherent and suspension HEK293 progeny cell lines suggest that the transition between adherent to suspension cell growth is not equivalent to the epithelial to mesenchymal transition even though several EMT-associated genes may be key to the difference between cell lines.
|
[
{
"end": 68,
"label": "CellLine",
"start": 62,
"text": "HEK293"
}
] |
ChemBL_V1
|
Instead key changes were found associated with cholesterol biosynthesis and fatty acid metabolism.
|
[] |
ChemBL_V1
|
For identification of key genes involved in the transition from adherent to suspension morphology, expression data from an additional set of 63 different human cell lines deposited in the Human Protein Atlas database were analyzed.
|
[] |
ChemBL_V1
|
Principal component analysis of these cell lines resulted in clustering of suspension cell lines in a distinct group separated from adherent cell lines (Fig. 6a).
|
[] |
ChemBL_V1
|
However, since most of the suspension cell lines are lymphoid or myeloid-derived this clustering may be a result of the similar origin of the suspension cell lines.
|
[] |
ChemBL_V1
|
Transcription data of the 38 previously identified differentially expressed genes from 47 adherent and 16 suspension cell lines (Supplementary Table S9) was compared between the two groups using a Mann–Whitney U-test.
|
[] |
ChemBL_V1
|
Within this set, nine genes (LOX, ID1, ADAMTS1, ZIC1, KCNMA1, DHRS3, RARG, COL4A6 and ARRDC4) had significant different expression levels between adherent and suspension cell lines with p-values < 0.01 (Fig. 6b,c).
|
[] |
ChemBL_V1
|
Four of these genes (ADAMTS1, KCNMA1, COL4A6 and ARRDC4) had the opposite directional change in the extended data set compared to the differential expression between only HEK293 strains.
|
[
{
"end": 177,
"label": "CellLine",
"start": 171,
"text": "HEK293"
}
] |
ChemBL_V1
|
Based on these findings, the remaining five genes (LOX, ID1, ZIC1, DHRS3 and RARG), which showed a consistent down-regulation in suspension cell lines compared to adherent cells, may play important roles in the morphological differences between the adherent and suspension cell lines.
|
[] |
ChemBL_V1
|
Figure 6Gene expression validation of the 38 previously identified differentially expressed genes in 63 human cell lines, identified nine significantly differentially expressed genes between suspension and adherent cell lines. (
|
[] |
ChemBL_V1
|
PCA transcriptomic data of 63 human cell-lines from the Human Protein Atlas shows a clear separation of suspension and adherent cell lines from different tissues. (
|
[] |
ChemBL_V1
|
Range of normalized counts in HPA cell lines for each of the previously identified 38 genes, differentially expressed between all adherent and suspension HEK293 cell lines.
|
[
{
"end": 160,
"label": "CellLine",
"start": 154,
"text": "HEK293"
}
] |
ChemBL_V1
|
The black line in each box shows median of normalized counts for the gene. (
|
[] |
ChemBL_V1
|
Genes that are differentially expressed between adherent and suspension cells using a Mann–Whitney U-test, with p-values < 0.01, are highlighted in purple, where length of bars shows logarithmic fold change of median between two groups and the color of bars denotes degree of significance of p-value.
|
[] |
ChemBL_V1
|
Non-significant genes have gray bars.
|
[] |
ChemBL_V1
|
Gene expression validation of the 38 previously identified differentially expressed genes in 63 human cell lines, identified nine significantly differentially expressed genes between suspension and adherent cell lines. (
|
[] |
ChemBL_V1
|
PCA transcriptomic data of 63 human cell-lines from the Human Protein Atlas shows a clear separation of suspension and adherent cell lines from different tissues. (
|
[] |
ChemBL_V1
|
Range of normalized counts in HPA cell lines for each of the previously identified 38 genes, differentially expressed between all adherent and suspension HEK293 cell lines.
|
[
{
"end": 160,
"label": "CellLine",
"start": 154,
"text": "HEK293"
}
] |
ChemBL_V1
|
The black line in each box shows median of normalized counts for the gene. (
|
[] |
ChemBL_V1
|
Genes that are differentially expressed between adherent and suspension cells using a Mann–Whitney U-test, with p-values < 0.01, are highlighted in purple, where length of bars shows logarithmic fold change of median between two groups and the color of bars denotes degree of significance of p-value.
|
[] |
ChemBL_V1
|
Non-significant genes have gray bars.
|
[] |
ChemBL_V1
|
Due to the extensive usage of HEK293 cells as a bioproduction platform for pharmaceutical proteins and AAV vectors, characterization of the HEK293 genome and transcriptome is relevant for bioprocess development.
|
[
{
"end": 36,
"label": "CellLine",
"start": 30,
"text": "HEK293"
},
{
"end": 146,
"label": "CellLine",
"start": 140,
"text": "HEK293"
}
] |
ChemBL_V1
|
A deeper knowledge of the HEK293 genomic and transcriptomic traits can for instance pave the way for more rational cell line engineering approaches, aiming to improve bioproduction efficiency and quality of protein products.
|
[
{
"end": 32,
"label": "CellLine",
"start": 26,
"text": "HEK293"
}
] |
ChemBL_V1
|
As different HEK293 lineages are propagated under different conditions and the observation that immortalized continuously cultured cell lines, such as HEK293, have a high degree of genomic instability with frequent chromosome rearrangements it can be expected that different HEK293 lineages are differentiated at the genomic and transcriptomic level compared to the parental cell line.
|
[
{
"end": 19,
"label": "CellLine",
"start": 13,
"text": "HEK293"
},
{
"end": 157,
"label": "CellLine",
"start": 151,
"text": "HEK293"
},
{
"end": 281,
"label": "CellLine",
"start": 275,
"text": "HEK293"
}
] |
ChemBL_V1
|
Here, the genomes and transcriptomes of the original HEK293 along with five progeny cell lineages were analyzed (Fig. 1a).
|
[
{
"end": 59,
"label": "CellLine",
"start": 53,
"text": "HEK293"
}
] |
ChemBL_V1
|
The overall comparison of genomic and transcriptomic profiles confirmed the picture of clonally diverged progeny cells as compared to the parental HEK293 (Fig. 1b,c).
|
[
{
"end": 153,
"label": "CellLine",
"start": 147,
"text": "HEK293"
}
] |
ChemBL_V1
|
As expected, there was a high degree of genomic and transcriptomic similarities of the Freestyle 293-F and 293-F cell lines (Fig. 1b–d).
|
[] |
ChemBL_V1
|
The results presented here indeed show that they are highly similar both on a genomic and transcriptomic level and confirm the previously reported findings that standard propagation of HEK293 cell lines does not alter the genomic profile to a large extent.
|
[
{
"end": 191,
"label": "CellLine",
"start": 185,
"text": "HEK293"
}
] |
ChemBL_V1
|
Furthermore, based on the hierarchical clustering, the adherent progeny cell lines showed a higher degree of divergence from each other compared to suspension cells.
|
[] |
ChemBL_V1
|
This may be a result of the independent transformation and isolation of the 293T and 293E lineages by the stable integration of different viral genes in different labs.
|
[
{
"end": 80,
"label": "CellLine",
"start": 76,
"text": "293T"
},
{
"end": 89,
"label": "CellLine",
"start": 85,
"text": "293E"
}
] |
ChemBL_V1
|
The relatively low expression level of EBNA1 observed in 293E cells may be an effect of cultivating cells in the absence of geneticin in this study, in order to minimize differences in cultivation conditions between cell lines.
|
[
{
"end": 61,
"label": "CellLine",
"start": 57,
"text": "293E"
}
] |
ChemBL_V1
|
Interestingly, a truncated version of the Large T antigen was also found to be expressed in 293E cells, which has to our knowledge not been reported previously (Fig. 1e and Supplementary Fig. S2).
|
[
{
"end": 96,
"label": "CellLine",
"start": 92,
"text": "293E"
}
] |
ChemBL_V1
|
This sequence was likely derived from the pRSVneo plasmid that was co-transfected with pCMV-EBNA1 during the isolation of the 293E c18 clone.
|
[] |
ChemBL_V1
|
The overall comparison of the genomic and transcriptomics profiles of HEK293 cell lines suggests that the parental HEK293 strain has the highest divergence amongst the cell lines.
|
[
{
"end": 76,
"label": "CellLine",
"start": 70,
"text": "HEK293"
},
{
"end": 121,
"label": "CellLine",
"start": 115,
"text": "HEK293"
}
] |
ChemBL_V1
|
Common changes in gene copy number gain or loss (Fig. 2 and Supplementary Fig. S3) and consensus differential expression alterations (Fig. 3) were observed amongst all progeny cell lines when compared to HEK293.
|
[
{
"end": 210,
"label": "CellLine",
"start": 204,
"text": "HEK293"
}
] |
ChemBL_V1
|
For instance, a common dense pattern of copy number gain and loss for progeny cell lines was observed on chromosome 13 and 18 (Fig. 2a).
|
[] |
ChemBL_V1
|
Such patterns, found across all or several lineages of HEK293 isolated independently by different methods, suggests a selective advantage for altered copy numbers of such loci in regard to the phenotypes of the cell lines.
|
[
{
"end": 61,
"label": "CellLine",
"start": 55,
"text": "HEK293"
}
] |
ChemBL_V1
|
On chromosome 13, several genes associated with the cytoskeleton (BORA, MZT1, PIBF1, DACH1 and KLHL1) had a copy number gain in all progeny cell lines (Supplementary Table S3).
|
[] |
ChemBL_V1
|
Indeed, consensus gene expression changes associated with cytoskeleton organization were observed between all progeny HEK293 cell lines and HEK293 (Fig. 3a).
|
[
{
"end": 124,
"label": "CellLine",
"start": 118,
"text": "HEK293"
},
{
"end": 146,
"label": "CellLine",
"start": 140,
"text": "HEK293"
}
] |
ChemBL_V1
|
In addition, BORA, MZT1 and DACH1 were found amongst the 329 genes commonly differentially expressed between all adherent and suspension cell lines (Supplementary Table S3).
|
[] |
ChemBL_V1
|
Moreover, amongst the five genes with high impact SNVs found in all progeny cell lines compared to HEK293, one gene (SGCD) encodes the cytoskeletal protein delta-sarcoglycan.
|
[] |
ChemBL_V1
|
Within the gained region of chromosome 18 common to all progeny cell lines except 293E, there are several cell adhesion molecules (DSC1, DSC2, DSC3, DSG1, DSG2, DSG3 and DSG4), which may render this region prone to gene copy number variation during cell line development.
|
[
{
"end": 86,
"label": "CellLine",
"start": 82,
"text": "293E"
}
] |
ChemBL_V1
|
The observed enrichment of cell adhesion GO-terms (GO:0,007,156 and GO:0,098,742) amongst genes with common high/moderate impact SNPs unique to progeny cell lines compared to HEK293 cells also supported common genomic alterations in progeny cell lines involved in cell adhesion.
|
[
{
"end": 181,
"label": "CellLine",
"start": 175,
"text": "HEK293"
}
] |
ChemBL_V1
|
Combined with the observed down-regulation of the entire cell adhesion gene set in progeny cell lines compared to HEK293 (Fig. 3a), results highlight changes in cytoskeleton and cell adhesion during continuous cultivation and cell line development of HEK293 cells.
|
[
{
"end": 120,
"label": "CellLine",
"start": 114,
"text": "HEK293"
},
{
"end": 257,
"label": "CellLine",
"start": 251,
"text": "HEK293"
}
] |
ChemBL_V1
|
Such traits associated with cell adhesion, cell motility and extracellular matrix organization may result from selective pressure, through inefficiency of detaching the most adherent cells, during single cell cloning.
|
[] |
ChemBL_V1
|
Indeed, the adherent progeny cell lines 293E and 293T are easier to detach by trypsinization compared to the parental HEK293, potentially through altered expression of cell adhesion, cytoskeletal and cell membrane proteins in accordance with the observed consensus changes between progeny cell lines and the parental HEK293.
|
[
{
"end": 44,
"label": "CellLine",
"start": 40,
"text": "293E"
},
{
"end": 53,
"label": "CellLine",
"start": 49,
"text": "293T"
},
{
"end": 124,
"label": "CellLine",
"start": 118,
"text": "HEK293"
},
{
"end": 323,
"label": "CellLine",
"start": 317,
"text": "HEK293"
}
] |
ChemBL_V1
|
Moreover, specific genomic regions of more local gain or loss of specific genes were observed, including a loss of fumarate hydratase (FH) gene copies.
|
[] |
ChemBL_V1
|
The loss of FH copies was previously observed for HEK293 by Lin and coworkers and was suggested to play an important part in the transformed phenotype of the cell line.
|
[
{
"end": 56,
"label": "CellLine",
"start": 50,
"text": "HEK293"
}
] |
ChemBL_V1
|
In line with this, our results showed that several of the HEK293 progeny cell lines (293E, 293-F and Freestyle 293-F) were found to only maintain half the number of FH gene copies compared to the original HEK293 (Supplementary Fig. S4), supporting an advantageous loss of the FH gene in the HEK293 cell lineages.
|
[
{
"end": 64,
"label": "CellLine",
"start": 58,
"text": "HEK293"
},
{
"end": 89,
"label": "CellLine",
"start": 85,
"text": "293E"
},
{
"end": 96,
"label": "CellLine",
"start": 91,
"text": "293-F"
},
{
"end": 110,
"label": "CellLine",
"start": 101,
"text": "Freestyle"
},
{
"end": 116,
"label": "CellLine",
"start": 111,
"text": "293-F"
},
{
"end": 211,
"label": "CellLine",
"start": 205,
"text": "HEK293"
},
{
"end": 297,
"label": "CellLine",
"start": 291,
"text": "HEK293"
}
] |
ChemBL_V1
|
Furthermore, a conserved pattern of substantial gain (> 1.5 log2-fold change) of the TLE4 gene and surrounding loci, was observed for all progeny cells except 293E (Supplementary Fig. S4).
|
[
{
"end": 163,
"label": "CellLine",
"start": 159,
"text": "293E"
}
] |
ChemBL_V1
|
Interestingly, TLE4 has previously been reported to have both a tumor suppressor function and to be associated with promoting tumor growth in different studies of different cancers.
|
[] |
ChemBL_V1
|
Moreover, a significant loss of the ADAM3A pseudogene (< -1 log2-fold change), which has previously been associated with different cancers, was observed in all progeny cell lines except 293-H compared to HEK293 (Supplementary Fig. S4).
|
[
{
"end": 191,
"label": "CellLine",
"start": 186,
"text": "293-H"
},
{
"end": 210,
"label": "CellLine",
"start": 204,
"text": "HEK293"
}
] |
ChemBL_V1
|
The specific gain of TLE4 and/or loss of ADAM3A loci and their association with tumor development, suggest important functions of these genes in the evolution of HEK293 cell lines, potentially through effects on proliferation and/or evasion of normal cell senescence of progeny cell lines.
|
[
{
"end": 168,
"label": "CellLine",
"start": 162,
"text": "HEK293"
}
] |
ChemBL_V1
|
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