Ameneiro Quiñoy, CristinaMoreira, Tiago MartinsFuentes Iglesias, AlejandroCortés Coego, AlbaGarcía Outeiral, VeraEscudero Pérez, AdrianaTorrecilla Cillero, DanielMulero Navarro, SoniaCarvajal González, José MaríaGuallar Artal, DianaFidalgo Pérez, Miguel Ángel2025-01-152025-01-152020-04-13Cristina Ameneiro, Tiago Moreira, Alejandro Fuentes-Iglesias, Alba Coego, Vera Garcia-Outeiral, Adriana Escudero, Daniel Torrecilla, Sonia Mulero-Navarro, Jose Maria Carvajal-Gonzalez, Diana Guallar, Miguel Fidalgo Life Science Alliance Apr 2020, 3 (5) e201900534; DOI: 10.26508/lsa.201900534https://hdl.handle.net/10347/38573BMAL1 is essential for the regulation of circadian rhythms in differentiated cells and adult stem cells, but the molecular underpinnings of its function in pluripotent cells, which hold a great potential in regenerative medicine, remain to be addressed. Here, using transient and permanent loss-of-function approaches in mouse embryonic stem cells (ESCs), we reveal that although BMAL1 is dispensable for the maintenance of the pluripotent state, its depletion leads to deregulation of transcriptional programs linked to cell differentiation commitment. We further confirm that depletion of Bmal1 alters the differentiation potential of ESCs in vitro. Mechanistically, we demonstrate that BMAL1 participates in the regulation of energy metabolism maintaining a low mitochondrial function which is associated with pluripotency. Loss-of-function of Bmal1 leads to the deregulation of metabolic gene expression associated with a shift from glycolytic to oxidative metabolism. Our results highlight the important role that BMAL1 plays at the exit of pluripotency in vitro and provide evidence implicating a non-canonical circadian function of BMAL1 in the metabolic control for cell fate determinationeng© 2020 Ameneiro et al. This article is available under a Creative Commons License Attribution 4.0 InternationalAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/BMAL1circadian rhythmsstem cellsmetabolism32 Ciencias médicasjournal article10.26508/lsa.2019005342575-1077open access