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Cell type-specific requirements for iPSC reprogramming

ABSTRACT: The differentiated state of somatic cells provides barriers for the efficient derivation of induced pluripotent stem cells (iPSCs). To address why some cell types reprogram more readily than others, we studied the effect of combined modulation of cellular signaling pathways. This revealed that inhibition of TGFβ together with activation of Wnt signaling in presence of ascorbic acid allows >80% of murine fibroblasts to acquire pluripotency after one week of reprogramming factor expression. In contrast, hepatic progenitors and blood progenitors predominantly required only TGFβ inhibition or canonical Wnt activation, respectively, to reprogram at efficiencies approaching 100%. Strikingly, blood progenitors reactivated endogenous pluripotency loci in a highly synchronous manner. We further demonstrate that expression of specific chromatin-modifying enzymes and reduced TGFβ/MAP kinase activity are intrinsic properties associated with the unique reprogramming response of these cells. Together, our observations define novel cell type-specific requirements for the rapid and synchronous reprogramming of somatic cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE59865 | GEO | 2014/09/11

SECONDARY ACCESSION(S): PRJNA256932

REPOSITORIES: GEO

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Cell type-specific requirements for iPSC reprogramming

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