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Altering metabolism to program cell identity via NAD+ dependent deacetylation [ATAC-seq]

GSE173542 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/04/01 Platform GPL19057
Summary
Cells change their metabolic profiles in response to an underling gene regulatory network, but how can alterations in metabolism encode specific transcriptional instructions?  Here we show that forcing metabolic change in embryonic stem cells (ESCs) promotes a developmental identity that better approximates the inner cell mass (ICM) of the mammalian blastocyst in cultures we refer to as enhanced metabolic ESCs (EMESCs).  The creation of EMESCs depends on the inhibition of glycolysis and stimulation of oxidative phosphorylation (OXPHOS), that in turns activates NAD+-dependent deacetlylases of the Sirtuin family.  The activation of this pathway leads to the deacetylation of histones and key transcription factors leading to a revised ICM-like gene regulatory network.  The exploitation of the NAD+/NADH coenzyme normally coupled to elevated OXPHOS to program lineage specific transcription suggests new paradigms for how cells respond to alterations in their environment.
Published in
Altering metabolism programs cell identity via NAD(+)-dependent deacetylation
Bone RA, Lowndes MP, Raineri S et al. · The EMBO journal 2025 · PMID 40281356 · doi:10.1038/s44318-025-00417-0
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Also filed as BioProject PRJNA726044 and SRA study SRP316856. Searching any of these in the dataset finder brings you back here.

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