PT - JOURNAL ARTICLE AU - Amador Gallardo AU - Aldara Molina AU - Helena G Asenjo AU - Jordi Martorell-Marugán AU - Rosa Montes AU - Verónica Ramos-Mejia AU - Antonio Sanchez-Pozo AU - Pedro Carmona-Sáez AU - Lourdes Lopez-Onieva AU - David Landeira TI - The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells AID - 10.26508/lsa.201900535 DP - 2020 May 01 TA - Life Science Alliance PG - e201900535 VI - 3 IP - 5 4099 - https://www.life-science-alliance.org/content/3/5/e201900535.short 4100 - https://www.life-science-alliance.org/content/3/5/e201900535.full SO - Life Sci. Alliance2020 May 01; 3 AB - Mammals optimize their physiology to the light–dark cycle by synchronization of the master circadian clock in the brain with peripheral clocks in the rest of the tissues of the body. Circadian oscillations rely on a negative feedback loop exerted by the molecular clock that is composed by transcriptional activators Bmal1 and Clock, and their negative regulators Period and Cryptochrome. Components of the molecular clock are expressed during early development, but onset of robust circadian oscillations is only detected later during embryogenesis. Here, we have used naïve pluripotent mouse embryonic stem cells (mESCs) to study the role of Bmal1 during early development. We found that, compared to wild-type cells, Bmal1−/− mESCs express higher levels of Nanog protein and altered expression of pluripotency-associated signalling pathways. Importantly, Bmal1−/− mESCs display deficient multi-lineage cell differentiation capacity during the formation of teratomas and gastrula-like organoids. Overall, we reveal that Bmal1 regulates pluripotent cell differentiation and propose that the molecular clock is an hitherto unrecognized regulator of mammalian development.