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Dose-resolved control of somatic reprogramming by Rora.

Haiyun Wang1, Yusha Li2, Chunkou Yin2

  • 1China-New Zealand Joint Laboratory on Biomedicine and Health, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative Medicine, Institute of Development and Regeneration, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong SAR, China.

Stem Cell Reports
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PubMed
Summary
This summary is machine-generated.

Nuclear receptors (NRs) regulate gene networks. The ROR subfamily, particularly Rora, enhances cell reprogramming in a dose-dependent manner, with moderate levels promoting and high levels inhibiting the process.

Keywords:
Roradose-dependent regulationnuclear receptorssomatic cell reprogramming

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Area of Science:

  • Cellular reprogramming
  • Gene regulation
  • Nuclear receptors

Background:

  • Nuclear receptors (NRs) are crucial transcription factors.
  • Their dosage and domains influence gene networks.
  • Understanding NR roles in cell reprogramming is vital.

Purpose of the Study:

  • To systematically profile murine NRs in OKS reprogramming.
  • To identify NR subfamilies that enhance reprogramming.
  • To elucidate the role of Rora in regulating cell-fate conversion.

Main Methods:

  • Systematic profiling of 49 murine NRs during OKS reprogramming.
  • Dose-response and domain dissection studies of Rora.
  • Analysis of interferon-gamma and WNT pathway modulation.

Main Results:

  • The ROR subfamily, especially Rora, enhances reprogramming.
  • Rora exhibits a dose-dependent, biphasic effect: moderate doses enhance, high doses inhibit.
  • Domain dissection revealed specific domains mediate pro-reprogramming and inhibitory effects.
  • Rora modulates reprogramming by affecting interferon-gamma and WNT signaling pathways.

Conclusions:

  • RORA acts as a dose- and domain-dependent regulator of cell reprogramming.
  • Nuclear receptor dosage control can be leveraged to improve reprogramming efficiency.
  • RORA coordinates chromatin and signaling pathways to gate cell-fate conversion.