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Characterization of distinct states of human naive pluripotency

ABSTRACT: The extent of naive characteriztics of recently reported naive human pluripotent stem cells (hPSCs) obtained in different naive-permissive media, is unclear. Moreover, these naive hPSCs were mainly derived by conversion from primed hPSCs or by direct derivation from human embryos rather than by somatic cell reprogramming. Here, we derived genetically matched human naive hPSCs by direct reprogramming of fibroblasts as well as primed-to-naive conversion using different naive conditions (NHSM, RSeT, 5iLAF and t2iLGöY). Comprehensive characterization showed that naive hPSCs obtained in these different conditions represent a spectrum of naive characteriztics irrespective of whether they were derived by conversion or reprograming. Importantly, only t2iLGöY hPSCs displayed a similar transcriptome to human cells from the inner cell mass, karyotypic stability and require re-priming for trilineage differentiation. Furthermore, our analyses identified KLF4 as a key reprogramming factor which enables conversion of primed hPSCs into naive t2iLGöY hPSCs. These findings underscore the role that reprogramming factors can play for the derivation of bona fide naive hPSCs and provide a molecular and functional reference for all the analysed conditions, which will help accelerate the downstream applications of naive hiPSCs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE102851 | GEO | 2017/09/25

SECONDARY ACCESSION(S): PRJNA399122

REPOSITORIES: GEO

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