USP9X deubiquitinase couples the pluripotency network and cell metabolism to regulate ESC differentiation potential
de Dieuleveult, M.; Leduc, M.; Salataj, E.; Ransy, C.; Dairou, J.; Homma, K.; Le Gall, M.; Bossard, P.; Lombes, A.; Bouillaud, F.; Ferry, L.; Defossez, P.-A.; Cadoret, J.-C.; Ichijo, H.; Wood, S. A.; Guillonneau, F.; Dressel, R.; Miotto, B.
Show abstract
Embryonic stem cells (ESC) have the unique ability to differentiate into all three germ cell layers. ESC transition through different states of pluripotency in response to growth factor signals and environmental cues before becoming terminally differentiated. Here, we demonstrated, by a multi-omic strategy, that the deubiquitinase USP9X regulates the developmental potential of ESC, and their transition from a naive to a more developmentally advance, or primed, state of pluripotency. We show that USP9X facilitates developmental gene expression and induces modifications of the mitochondrial bioenergetics, including decreased routing of pyruvate towards its oxidation and reduced respiration. In addition, USP9X binds to the pluripotency factor ESRRB, regulates its abundance and the transcriptional levels of a subset of its target genes. Finally, under permissive culture conditions, depletion of Usp9X accelerates cell differentiation in all cell lineages. We thus identified a new regulator of naive pluripotency and show that USP9X couples ESRRB pluripotency transcriptional network and cellular metabolism, both of which are important for ESC fate and pluripotency.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- miR-183/96/182 cluster is an important morphogenetic factor targeting PAX6 expression in differentiating human retinal organoids 94%
- Constitutive high expression of NOXA sensitizes human embryonic stem cells for rapid cell death 94%
- Unlocking cellular plasticity: Enhancing human iPSC reprogramming through bromodomain inhibition and extracellular matrix gene expression regulation 94%
Similar papers in this journal
- OTX2 controls chromatin accessibility to direct somatic versus germline differentiation 96%
- Lgr5 Controls Extracellular Matrix Production By Stem Cells In The Developing Intestine 93%
- A novel role for the peptidyl-prolyl cis-trans isomerase Cyclophilin A in DNA-repair following replication fork stalling via the MRE11-RAD50-NBS1 complex. 92%
Similar papers in this journal
- Anabolic Factors and Myokines Improve Differentiation of Human Embryonic Stem Cell Derived Skeletal Muscle Cells 94%
- Transcription factor-mediated generation of dopaminergic neurons from human iPSCs: a comparison of methods 93%
- Impaired p53-mediated DNA damage response contributes to microcephaly in Nijmegen Breakage Syndrome patient-derived cerebral organoids 93%
Similar papers in this journal
- A sub-set of guanine- and cytosine-rich genes are actively transcribed at the nuclear Lamin B1 region 95%
- The efficient induction of human retinal ganglion-like cells provides a platform for studying optic neuropathies 93%
- Rhes, a Striatal Enriched Protein, Regulates Post-Translational Small-Ubiquitin-like-Modifier (SUMO) Modification of Nuclear Proteins and Alters Gene Expression 93%
Similar papers in this journal
- Canonical Wnt pathway controls mESCs self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions 95%
- Prosaposin maintains adult neural stem cells in a state associated with deep quiescence 94%
- Toti: an integrated multi-omics database to decipher the epigenetic regulation of gene expression in totipotent stem cells 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.