RT Journal Article
SR Electronic
T1 The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900535
DO 10.26508/lsa.201900535
VO 3
IS 5
A1 Amador Gallardo
A1 Aldara Molina
A1 Helena G Asenjo
A1 Jordi Martorell-Marugán
A1 Rosa Montes
A1 Verónica Ramos-Mejia
A1 Antonio Sanchez-Pozo
A1 Pedro Carmona-Sáez
A1 Lourdes Lopez-Onieva
A1 David Landeira
YR 2020
UL https://www.life-science-alliance.org/content/3/5/e201900535.abstract
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.