Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming

作者:Liu, Xiaodong; Nefzger, Christian M.; Rossello, Fernando J.; Chen, Joseph; Knaupp, Anja S.; Firas, Jaber; Ford, Ethan; Pflueger, Jahnvi; Paynter, Jacob M.; Chy, Hun S.; O'Brien, Carmel M.; Huang, Cheng; Mishra, Ketan; Hodgson-Garms, Margeaux; Jansz, Natasha; Williams, Sarah M.; Blewitt, Marnie E.; Nilsson, Susan K.; Schittenhelm, Ralf B.; Laslett, Andrew L.; Lister, Ryan; Polo, Jose M.
来源:Nature Methods, 2017, 14(11): 1055-+.
DOI:10.1038/NMETH.4436

摘要

Recent reports on the characteristics of naive human pluripotent stem cells (hPSCs) obtained using independent methods differ. Naive hPSCs have been mainly derived by conversion from primed hPSCs or by direct derivation from human embryos rather than by somatic cell reprogramming. To provide an unbiased molecular and functional reference, we derived genetically matched naive hPSCs by direct reprogramming of fibroblasts and by primed-to-naive conversion using different naive conditions (NHSM, RSeT, 5iLAF and t2iLGoY). Our results show that hPSCs obtained in these different conditions display a spectrum of naive characteristics. Furthermore, our characterization identifies KLF4 as sufficient for conversion of primed hPSCs into naive t2iLGoY hPSCs, underscoring the role that reprogramming factors can play for the derivation of bona fide naive hPSCs.