RT Journal Article
T1 BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells
A1 Ameneiro Quiñoy, Cristina
A1 Moreira, Tiago Martins
A1 Fuentes Iglesias, Alejandro
A1 Cortés Coego, Alba
A1 García Outeiral, Vera
A1 Escudero Pérez, Adriana
A1 Torrecilla Cillero, Daniel
A1 Mulero Navarro, Sonia
A1 Carvajal González, José María
A1 Guallar Artal, Diana
A1 Fidalgo Pérez, Miguel Ángel
K1 BMAL1
K1 circadian rhythms
K1 stem cells
K1 metabolism
AB BMAL1 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 determination
PB Life Science Alliance
YR 2020
FD 2020-04-13
LK https://hdl.handle.net/10347/38573
UL https://hdl.handle.net/10347/38573
LA eng
NO Cristina 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.201900534
DS Minerva
RD 24 abr 2026