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

Xiaodong Liu^{1

2

3}, Christian M Nefzger^{1

2

3}, Fernando J Rossello^{1

2

3}, Joseph Chen^{1

2

3}, Anja S Knaupp^{1

2

3}, Jaber Firas^{1

2

3}, Ethan Ford^{4

5}, Jahnvi Pflueger^{4

5}, Jacob M Paynter^{1

2

3}, Hun S Chy^{3

6}, Carmel M O'Brien^{3

6}, Cheng Huang⁷, Ketan Mishra^{1

2

3}, Margeaux Hodgson-Garms^{1

2

3}, Natasha Jansz^{8

9}, Sarah M Williams^{1

2

3

10}, Marnie E Blewitt^{8

9}, Susan K Nilsson^{3

6}, Ralf B Schittenhelm⁷, Andrew L Laslett^{3

6}, Ryan Lister^{4

5}, Jose M Polo^{1

2

3}

Affiliations

¹ Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, Victoria, Australia.
² Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, Victoria, Australia.
³ Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, Victoria, Australia.
⁴ ARC Center of Excellence in Plant Energy Biology, The University of Western Australia, Perth, Western Australia, Australia.
⁵ The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.
⁶ Manufacturing, CSIRO, Clayton, Victoria, Australia.
⁷ Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
⁸ The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
⁹ University of Melbourne, Melbourne, Victoria, Australia.
¹⁰ Monash Bioinformatics Platform, Monash University, Wellington Road, Clayton, Victoria, Australia.

PMID: 28945704
DOI: 10.1038/nmeth.4436

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

Xiaodong Liu et al. Nat Methods. 2017 Nov.

. 2017 Nov;14(11):1055-1062.

doi: 10.1038/nmeth.4436. Epub 2017 Sep 25.

Authors

Affiliations

¹ Department of Anatomy and Developmental Biology, Monash University, Wellington Road, Clayton, Victoria, Australia.
² Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Wellington Road, Clayton, Victoria, Australia.
³ Australian Regenerative Medicine Institute, Monash University, Wellington Road, Clayton, Victoria, Australia.
⁴ ARC Center of Excellence in Plant Energy Biology, The University of Western Australia, Perth, Western Australia, Australia.
⁵ The Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.
⁶ Manufacturing, CSIRO, Clayton, Victoria, Australia.
⁷ Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
⁸ The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
⁹ University of Melbourne, Melbourne, Victoria, Australia.
¹⁰ Monash Bioinformatics Platform, Monash University, Wellington Road, Clayton, Victoria, Australia.

PMID: 28945704
DOI: 10.1038/nmeth.4436

Abstract

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.

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

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

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