Dose-resolved control of somatic reprogramming by Rora

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.