Zhang, Zhi-BoSinha, JoydebBahrami-Nejad, ZahraTeruel, Mary N.2021-12-202021-12-202021https://hdl.handle.net/1813/110377The circadian clock is known to regulate cell differentiation, but how continuous daily oscillations control a much longer, multi-day differentiation process is not known. Here we monitor the circadian clock and progression of adipocyte differentiation in live cells. Strikingly, we find that cells preferentially commit to differentiate during a 12-hour window each day that corresponds to the time of rest. We show that daily gating of differentiation occurs because irreversible commitment to differentiate occurs within a few hours, much faster than the 12-hour circadian clock gating window and the overall multi-day differentiation process. The resulting circadian bursts of differentiation are driven by clock-driven expression of CEBPA, which is in a fast positive feedback relationship with PPARG, the master regulator of adipogenesis. Our findings are of broad relevance given that most differentiating somatic cells have an intrinsic circadian clock that regulates differentiation.en-USdataset