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 Laslett; Ryan Lister; Jose M Polo

doi:10.1038/nmeth.4436

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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116 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1055-1062
Number of pages	8
Journal	Nature Methods
Volume	14
Issue number	11
DOIs	https://doi.org/10.1038/nmeth.4436
Publication status	Published - 31 Oct 2017

Keywords

biological models
embryonic stem cells
pluripotent stem cells
reprogramming

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10.1038/nmeth.4436

225801294-oaFinal published version, 3.78 MB

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Liu, X., Nefzger, C. M., Rossello, F. J., Chen, J., Knaupp, A. S., Firas, J., Ford, E., Pflueger, J., Paynter, J. M., Chy, H. S., O'Brien, C. M., Huang, C., Mishra, K., Hodgson-Garms, M., Jansz, N., Williams, S. M., Blewitt, M. E., Nilsson, S. K., Schittenhelm, R. B., ... Polo, J. M. (2017). Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming. Nature Methods, 14(11), 1055-1062. https://doi.org/10.1038/nmeth.4436

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title = "Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming",

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 t2iLG{\"o}Y). 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 t2iLG{\"o}Y hPSCs, underscoring the role that reprogramming factors can play for the derivation of bona fide naive hPSCs.",

keywords = "biological models, embryonic stem cells, pluripotent stem cells, reprogramming",

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

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Liu, X, Nefzger, CM, Rossello, FJ, Chen, J, Knaupp, AS, Firas, J, Ford, E, Pflueger, J, Paynter, JM, Chy, HS, O'Brien, CM, Huang, C, Mishra, K, Hodgson-Garms, M, Jansz, N, Williams, SM, Blewitt, ME, Nilsson, SK , Schittenhelm, RB , Laslett, AL, Lister, R & Polo, JM 2017, 'Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming', Nature Methods, vol. 14, no. 11, pp. 1055-1062. https://doi.org/10.1038/nmeth.4436

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AU - Liu, Xiaodong

AU - Nefzger, Christian M

AU - Rossello, Fernando J

AU - Chen, Joseph

AU - Knaupp, Anja S

AU - Firas, Jaber

AU - Ford, Ethan

AU - Pflueger, Jahnvi

AU - Paynter, Jacob M

AU - Chy, Hun S

AU - O'Brien, Carmel M

AU - Huang, Cheng

AU - Mishra, Ketan

AU - Hodgson-Garms, Margeaux

AU - Jansz, Natasha

AU - Williams, Sarah M

AU - Blewitt, Marnie E

AU - Nilsson, Susan K

AU - Schittenhelm, Ralf B

AU - Laslett, Andrew L

AU - Lister, Ryan

AU - Polo, Jose M

PY - 2017/10/31

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AB - 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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JF - Nature Methods

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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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