RT Journal Article
T1 The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells
A1 Gallardo, Amador
A1 Molina, Aldara
A1 Asenjo, Helena G.
A1 Martorell-Marugán, Jordi
A1 Montes, Rosa
A1 Ramos-Mejia, Verónica
A1 Sanchez-Pozo, Antonio
A1 Carmona-Sáez, Pedro
A1 Lopez-Onieva, Lourdes
A1 Landeira, David
K1 ARNTL transcription factors
K1 Clock proteins
K1 Circadian clocks
K1 Cryptochromes
K1 Gene expression
K1 Pluripotent stem cells
K1 Factores de transcripción ARNTL
K1 Proteínas clock
K1 Relojes circadianos
K1 Criptocromos
K1 Expresión genética
K1 Células madre pluripotentes
K1 Mice
K1 Ratones
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.
PB Life Science Alliance LLC
YR 2020
FD 2020-04-13
LK http://hdl.handle.net/10668/3495
UL http://hdl.handle.net/10668/3495
LA en
NO Gallardo A, Molina A, Asenjo HG, Martorell-Marugán J, Montes R, Ramos-Mejia V, et al. The molecular clock protein Bmal1 regulates cell differentiation in mouse embryonic stem cells. Life Sci Alliance. 2020 Apr 13;3(5):e201900535.
DS RISalud
RD Apr 5, 2025