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

Xiaodong Liu, Christian M Nefzger, Fernando J Rossello, Joseph Chen, Anja S Knaupp, Jaber Firas, Ethan Ford, Jahnvi Pflueger, Jacob M Paynter, Hun S Chy, Carmel M O'Brien, Cheng Huang, Ketan Mishra, Margeaux Hodgson-Garms, Natasha Jansz, Sarah M Williams, Marnie E Blewitt, Susan K Nilsson, Ralf B Schittenhelm, Andrew L LaslettRyan Lister, Jose M Polo

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79 Citations (Scopus)


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 t2iLGöY). 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 t2iLGöY hPSCs, underscoring the role that reprogramming factors can play for the derivation of bona fide naive hPSCs.

Original languageEnglish
Pages (from-to)1055-1062
Number of pages8
JournalNature Methods
Issue number11
Publication statusPublished - 31 Oct 2017


  • biological models
  • embryonic stem cells
  • pluripotent stem cells
  • reprogramming

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