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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120 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 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.

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 - Nov 2017

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10.1038/NMETH.4436

Repair of Epigenetic Abnormalities in Human Induced Pluripotent Stem Cells by Targeted Epigenome Engineering
Lister, R. (Investigator 01), Polo, J. (Investigator 02), Swaminatha Iyer, I. (Investigator 03) & Blancafort, P. (Investigator 04)
NHMRC National Health and Medical Research Council
1/01/14 → 31/12/16
Project: Research

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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

@article{d8f22bbe8a2d479dadf56e32b8c481de,

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 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.",

keywords = "EMBRYONIC STEM-CELLS, RNA-SEQ, GENE-EXPRESSION, WEB TOOL, HUMAN ES, IDENTIFICATION, VISUALIZATION, BLASTOCYST, INDUCTION, CIRCUITRY",

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.}",

year = "2017",

month = nov,

doi = "10.1038/NMETH.4436",

language = "English",

volume = "14",

pages = "1055--1062",

journal = "Nature Methods",

issn = "1548-7091",

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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

TY - JOUR

T1 - Comprehensive characterization of distinct states of human naive pluripotency generated by reprogramming

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 - 2017/11

Y1 - 2017/11

N2 - 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.

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 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.

KW - EMBRYONIC STEM-CELLS

KW - RNA-SEQ

KW - GENE-EXPRESSION

KW - WEB TOOL

KW - HUMAN ES

KW - IDENTIFICATION

KW - VISUALIZATION

KW - BLASTOCYST

KW - INDUCTION

KW - CIRCUITRY

U2 - 10.1038/NMETH.4436

DO - 10.1038/NMETH.4436

M3 - Article

SN - 1548-7091

VL - 14

SP - 1055

EP - 1062

JO - Nature Methods

JF - Nature Methods

IS - 11

ER -

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

Abstract

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Repair of Epigenetic Abnormalities in Human Induced Pluripotent Stem Cells by Targeted Epigenome Engineering

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