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Transcript abundance in A-T-derived iPSC: Comparing isogenic cells to unrelated individual

ABSTRACT: Induced pluripotent stem cells (iPSC) were prepared from multiple subjects with Ataxia-telangiectasia (A-T). iPSC were prepared from activated T-cells using commercial Sendai virus to deliver reprogramming factors. ATM protein-expressing and non-expressing cultures would found in multiple sub-lines (sub-lines are generated from distinct founder colonies of cells) from a single subject (Q3). Genetic analysis determined that all sub-lines originated from the same subject and were likely the product of spontaneous reversion by gene correction. To compare gene expression profiles, three iPSC samples were assayed: (1) A reverted ATM+/- subline from subject Q3, (2) An ATM-/- subline from subject Q3, and (3) An iPSC line from an unrelated ATM-/- subject, Q1. Analysis reveals that the majority of significantly-different genes between the unrelated ATM-/- line (Q1SA) and the reverted ATM+/- line (Q3SC) was due to genetic variation between individuals. A more focused set of contrasting genes could be identified between the isogenic Q3-derived lines (Q3SA, ATM-/-, vs. Q3SC, ATM+/-). The 206 transcripts that are significantly different point to a differential regulation of p53-associated pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71878 | GEO | 2015/11/19

SECONDARY ACCESSION(S): PRJNA292390

REPOSITORIES: GEO

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Transcript abundance in A-T-derived iPSC: Comparing isogenic cells to unrelated individual

Project description:Induced pluripotent stem cells (iPSC) were prepared from multiple subjects with Ataxia-telangiectasia (A-T). iPSC were prepared from activated T-cells using commercial Sendai virus to deliver reprogramming factors. ATM protein-expressing and non-expressing cultures would found in multiple sub-lines (sub-lines are generated from distinct founder colonies of cells) from a single subject (Q3). Genetic analysis determined that all sub-lines originated from the same subject and were likely the product of spontaneous reversion by gene correction. To compare gene expression profiles, three iPSC samples were assayed: (1) A reverted ATM+/- subline from subject Q3, (2) An ATM-/- subline from subject Q3, and (3) An iPSC line from an unrelated ATM-/- subject, Q1. Analysis reveals that the majority of significantly-different genes between the unrelated ATM-/- line (Q1SA) and the reverted ATM+/- line (Q3SC) was due to genetic variation between individuals. A more focused set of contrasting genes could be identified between the isogenic Q3-derived lines (Q3SA, ATM-/-, vs. Q3SC, ATM+/-). The 206 transcripts that are significantly different point to a differential regulation of p53-associated pathways. Total cellular RNA was prepared from each iPSC culture. Different passage numbers or sister cultures were used as replicates (n=2).

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