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Temporal activation of LRH‐1 and RAR‐γ in human pluripotent stem cells induces a functional naïve‐like state
Author(s) -
Taei Adeleh,
Kiani Tahereh,
Taghizadeh Zeinab,
Moradi Sharif,
Samadian Azam,
Mollamohammadi Sepideh,
SharifiZarchi Ali,
Guenther Stefan,
Akhlaghpour Azimeh,
Asgari Abibeiglou Behrouz,
NajarAsl Mostafa,
Karamzadeh Razieh,
Khalooghi Keynoosh,
Braun Thomas,
Hassani SeyedehNafiseh,
Baharvand Hossein
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201847533
Subject(s) - induced pluripotent stem cell , reprogramming , microbiology and biotechnology , biology , retinoic acid , signal transduction , transcription factor , cellular differentiation , embryonic stem cell , cell , cell culture , genetics , gene
Naïve pluripotency can be established in human pluripotent stem cells (hPSCs) by manipulation of transcription factors, signaling pathways, or a combination thereof. However, differences exist in the molecular and functional properties of naïve hPSCs generated by different protocols, which include varying similarities with pre‐implantation human embryos, differentiation potential, and maintenance of genomic integrity. We show here that short treatment with two chemical agonists (2a) of nuclear receptors, liver receptor homologue‐1 (LRH‐1) and retinoic acid receptor gamma (RAR‐γ), along with 2i/LIF (2a2iL) induces naïve‐like pluripotency in human cells during reprogramming of fibroblasts, conversion of pre‐established hPSCs, and generation of new cell lines from blastocysts. 2a2iL‐hPSCs match several defined criteria of naïve‐like pluripotency and contribute to human–mouse interspecies chimeras. Activation of TGF‐β signaling is instrumental for acquisition of naïve‐like pluripotency by the 2a2iL induction procedure, and transient activation of TGF‐β signaling substitutes for 2a to generate naïve‐like hPSCs. We reason that 2a2iL‐hPSCs are an easily attainable system to evaluate properties of naïve‐like hPSCs and for various applications.