1. Epigenetic and Transcriptional Shifts in Human Neural Stem Cells after Reprogramming into Induced Pluripotent Stem Cells and Subsequent Redifferentiation.
- Author
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Haubenreich, Carolin, Lenz, Michael, Schuppert, Andreas, Peitz, Michael, Koch, Philipp, Zenke, Martin, and Brüstle, Oliver
- Subjects
PLURIPOTENT stem cells ,INDUCED pluripotent stem cells ,HUMAN stem cells ,NEURAL stem cells ,SOMATIC cells ,GENE expression ,P16 gene - Abstract
Induced pluripotent stem cells (iPSCs) and their derivatives have been described to display epigenetic memory of their founder cells, as well as de novo reprogramming-associated alterations. In order to selectively explore changes due to the reprogramming process and not to heterologous somatic memory, we devised a circular reprogramming approach where somatic stem cells are used to generate iPSCs, which are subsequently re-differentiated into their original fate. As somatic founder cells, we employed human embryonic stem cell-derived neural stem cells (NSCs) and compared them to iPSC-derived NSCs derived thereof. Global transcription profiling of this isogenic circular system revealed remarkably similar transcriptomes of both NSC populations, with the exception of 36 transcripts. Amongst these we detected a disproportionately large fraction of X chromosomal genes, all of which were upregulated in iPSC-NSCs. Concurrently, we detected differential methylation of X chromosomal sites spatially coinciding with regions harboring differentially expressed genes. While our data point to a pronounced overall reinstallation of autosomal transcriptomic and methylation signatures when a defined somatic lineage is propagated through pluripotency, they also indicate that X chromosomal genes may partially escape this reinstallation process. Considering the broad application of iPSCs in disease modeling and regenerative approaches, such reprogramming-associated alterations in X chromosomal gene expression and DNA methylation deserve particular attention. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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