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  • ÀúÀÚCristina Ameneiro, Tiago Moreira, Alejandro Fuentes-Iglesias, Alba Coego, Vera Garcia-Outei
  • ÃâÆÇ»ç¾ÆÁø
  • ÃâÆÇÀÏ2020-07-12
  • µî·ÏÀÏ2020-12-21
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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-offunction 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.
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BMAL1 coordinates energy metabolism and differentiation of
pluripotent stem cells

1. Introduction 23
2. Results 24
3. BMAL1 is required for exiting pluripotency in vitro 26
4. Discussion 31
5. Materials and Methods 32
6. Mesendoderm differentiation assay 34
7. Data Availability 35
8. References 35

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