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Temporal activation of LRH-1 and RAR-γ in human pluripotent stem cells induces a functional naïve-like state
, Article EMBO Reports ; Volume 21, Issue 10 , 2020 ; Kiani, T ; Taghizadeh, Z ; Moradi, S ; Samadian, A ; Mollamohammadi, S ; Sharifi Zarchi, A ; Guenther, S ; Akhlaghpour, A ; Asgari Abibeiglou, B ; Najar Asl, M ; Karamzadeh, R ; Khalooghi, K ; Braun, T ; Hassani, S. N ; Baharvand, H ; Sharif University of Technology
Wiley-VCH Verlag
2020
Abstract
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,...