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Accession IconSRP049340

Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency [mRNA-Seq]

Organism Icon Homo sapiens
Sample Icon 166 Downloadable Samples
Technology Badge IconIllumina HiSeq 2500, Illumina HiSeq 2000

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Description
Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered re-activation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. Overall design: mRNA sequencing of primary and secondary fibroblasts with reference BJ (supplementary file fibroblasts), reprogramming intermendiates from untreated hiF-T reprogramming (supplementary file reprogramming), or selective time points upon LSD1 inhibitor treatment (supplementary file LSD1i). RNA samples used for mRNA sequencing are the same used for smallRNA sequencing.
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166
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