Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition

ABSTRACT: Pluripotent stem cells (PSCs), which include embryonic stem cells (ESCs) derived from embryos and induced pluripotent stem cells (iPSCs) reprogrammed from somatic cells, possess significant application potential due to their ability to indefinitely self-renew while maintaining pluripotency. However, many aspects of PSC fate transitions remain poorly understood. Hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) by deficiency of its upstream repressors TSC1/2 is known to impede both pluripotency re-establishment and exit. Yet, the detailed mechanism by which mTORC1 regulates transcription critical for these transitions, and whether similar mechanisms underlie both processes, remains unclear. In this study, we demonstrate that mTORC1 induces the nuclear translocation of transcription factor TFE3, which binds to the nucleosome remodeling and deacetylation complex NuRD. This interaction leads to the repression of specific target genes crucial for pluripotency re-establishment and exit. Our findings highlight that the mTORC1-TFE3-NuRD axis acts as a transcriptional repressor in PSC fate transitions through regulation of chromatin remodeling modifications. These findings contribute to a better understanding of how mTORC1 governs the intricate regulation of PSC fate transitions, which is relevant to diverse fields including development, metabolic diseases, cancer, and aging.

ORGANISM(S): Mus musculus

PROVIDER: GSE273086 | GEO | 2025/07/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

mTORC1 hyperactivation blocks pluripotent stem cells fate transitions through TFE3-NuRD association [CUT&Tag]

Project description:As an evolutionarily conserved master regulator of metabolism, mechanistic target of rapamycin complex 1 (mTORC1) regulates cell states and fates in development, cancer and aging. mTORC1 activity regulation was critical for pluripotent stem cells maintenance and cell fate transitions. Inhibition of mTORC1 induces embryonic stem cells (ESCs) entry into a paused state which reversibly arrests self-renewal leaving pluripotency intact. Hyperactivation of mTORC1 impedes both pluripotency re-establishment and exit of PSCs. As shown that mTORC1 mediates TFE3 nuclear translocation block pluripotency exit, whether similar mechanisms through transcription factor TFE3 are involved in these processes, and the detailed mechanism by which mTORC1-TFE3 regulates critical transcriptional processes for these transitions, remain unclear. In this study, we demonstrate that the nuclear translocation of TFE3, induced by hyperactivation of mTORC1, results in its binding to the nucleosome remodeling and deacetylation (NuRD) complex in both re-establishment and exit of pluripotency. This interaction inhibits the expression of various crucial genes during different fate transitions of PSCs. Our findings uncover a common and key role of TFE3-NuRD association as mediator of mTORC1 to block pluripotent cell fate transitions, with implications for various fields including physiological and pathological diseases.

2024-08-13 | GSE274330 | GEO

mTORC1 hyperactivation blocks pluripotent stem cells fate transitions through TFE3-NuRD association [RNA-Seq]

2024-08-13 | GSE274328 | GEO

mTORC1 hyperactivation blocks pluripotent stem cells fate transitions through TFE3-NuRD association

2025-07-09 | GSE301743 | GEO

Folliculin regulates mTORC1/2 and WNT pathways in early human pluripotency

Project description:It is important to understand how cells can maintain and exit human pluripotency. We exploited the metabolic and epigenetic differences between naïve and primed pluripotent cells to design a CRISPR-Cas9 screen for identifying genes that promote the exit from naïve pluripotency. Among the known and novel regulators of this early step of human development, we identified the tumor suppressor folliculin (FLCN). Flcn is important for implantation of the mouse embryo into the uterus and has been shown to regulate the exit of pluripotency in mouse through activation of Esrrb. However, the function of FLCN is unknown in human embryonic stem cells (hESC). Knock-out (KO) of FLCN revealed that it is not essential to maintain the naïve pluripotent state but is required for the exit of that state, in part by controlling the localization of the transcription factor TFE3. While mainly found in the cytoplasm of cells exiting the naïve state, FLCN KO resulted in TFE3 nuclear localization. TFE3 targets up-regulated in FLCN KO exit assay were members of Wnt pathway and ESRRB. Treatment of FLCN KO hESC with a Wnt inhibitor rescued the phenotype and allowed the cells to exit the naïve state. In contrast, the lack of rescue in ESRRB/FLCN double KO lines suggested that ESRRB was not responsible for the FLCN mutant phenotype. Using co-immunoprecipitation and mass spectrometry analysis we identified unique FLCN binding partners, in addition to known FLCN interactors, at various stages of pluripotency. The interactions of FLCN with components of the mTOR pathway (mTORC1 and mTORC2) revealed a mechanism of FLCN function during exit from naïve pluripotency.

2018-11-03 | GSE122118 | GEO

Mus musculus

Project description:The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition[CUT&Tag]

| PRJNA1139367 | ENA

Mus musculus

Project description:The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition [CUT&Tag]

| PRJNA1142898 | ENA

Project description:The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition [CUT&Tag]

| PRJNA1256719 | ENA

Global Profiling of the Lysine Crotonylome in Different Pluripotent States

Project description:Understanding the mechanisms of pluripotency maintenance and exit are important for developmental biology and regenerative medicine. However, studies of pluripotency and post-translational modifications of proteins are scarce. To systematically profile protein crotonylation in mouse pluripotent stem cells (PSCs) in different culture conditions, we used affinity purification of crotonylated peptides, TMT labeling, and LC-MS/MS. Our study included PSCs in ground, metastable, and primed state, as well as metastable PSCs undergoing early pluripotency exit. We have successfully identified 8,102 crotonylation sites in 2,578 proteins, among which 3,628 sites in 1,426 proteins were with high-confidence. These high-confidence crotonylated proteins are enriched for factors involved in functions related to pluripotency such as RNA biogenesis, central carbon metabolism, and proteasome function. Our atlas of protein crotonylation will be valuable for further studies of pluripotency regulation and may also provide insights into the role of crotonylation in other cell fate transitions.

2021-02-26 | PXD017121 | Pride

Mus musculus

Project description:The mTORC1-TFE3-NuRD axis mediates pluripotent stem cells fate transition[bulk RNA-Seq]

| PRJNA1139377 | ENA

Modeling signaling-dependent pluripotent cell states with boolean logic can predict cell fate transitions [I]

Project description:Pluripotent stem cells (PSCs) exist in multiple stable states, each with specific cellular properties and molecular signatures. The process by which pluripotency is either maintained or destabilized to initiate specific developmental programs is poorly understood. We have developed a model to predict stabilized PSC gene regulatory network (GRN) states in response to combinations of input signals. While previous attempts to model PSC fate have been limited to static cell compositions, our approach enables simulations of dynamic heterogeneity by combining an Asynchronous Boolean Simulation (ABS) strategy with simulated single cell fate transitions using a Strongly Connected Components (SCCs). This computational framework was applied to a reverse-engineered and curated core GRN for mouse embryonic stem cells (mESCs) to simulate responses to LIF, Wnt/β-catenin, FGF/ERK, BMP4, and Activin A/Nodal pathway activation. For these input signals, our simulations exhibit strong predictive power for gene expression patterns, cell population composition, and nodes controlling cell fate transitions. The model predictions extend into early PSC differentiation, demonstrating, for example, that a Cdx2-high/Oct4-low state can be efficiently generated from mESCs residing in a naïve and signal-receptive state sustained by combinations of signaling activators and inhibitors.

2018-02-06 | GSE88926 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data