Temporal activation of LRH-1 and RAR-γ in human pluripotent stem cells induces a functional naïve-like state

Taei, A ; Sharif University of Technology | 2020

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  1. Type of Document: Article
  2. DOI: 10.15252/embr.201847533
  3. Publisher: Wiley-VCH Verlag , 2020
  4. Abstract:
  5. 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. © 2020 The Authors
  6. Keywords:
  7. Chimera formation ; Human naïve pluripotency ; Nuclear receptors ; TGF-β signaling pathway ; Liver receptor homolog 1 ; Retinoic acid receptor gamma ; Tansforming growth factor beta ; Animal cell ; Animal tissue ; Blastocyst ; Chimera ; Controlled study ; Embryo ; Human ; Human cell ; Mouse ; Nonhuman ; Nuclear reprogramming ; Pluripotent stem cell ; Priority journal ; Skin fibroblast ; TGF beta signaling
  8. Source: EMBO Reports ; Volume 21, Issue 10 , 2020
  9. URL: https://www.embopress.org/doi/abs/10.15252/embr.201847533