Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [RNA-seq]

ABSTRACT: Histone modifiers instruct cellular differentiation, yet how they achieve temporal precision remains enigmatic. Here we demonstrate that the H3K27 demethylase Kdm6b acts as a master epigenetic conductor and achieves timed gene activation by sequentially partnering with stage-specific transcription factors (TFs) in motor neuron (MN) differentiation. Genome-wide profiling revealed Kdm6b occupancy progressively shifted from proximal promoters to distal enhancers, along with increasing regulatory elements during maturation. At occupied sites, Kdm6b triggered rapid H3K27me3 loss with concurrent H3K27ac/H3K4me1 gain, establishing activation-competent chromatin. By integrating developmental TFs and histone modification landscapes, Kdm6b builds up the dynamic epigenetic choreography to precisely regulate MN developmental programs from early MN fate specification, intermediate cell differentiation and growth to later maturation. The ordered expression of developmental genes was compromised by stage-specific Kdm6b inhibition. Our work resolves how a single epigenetic regulator achieves temporal precision in driving stepwise MN development, with broad implications for neurodevelopment and diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE305767 | GEO | 2025/09/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [CutRun_CutTag]

Project description:Histone modifiers instruct cellular differentiation, yet how they achieve temporal precision remains enigmatic. Here we demonstrate that the H3K27 demethylase Kdm6b acts as a master epigenetic conductor and achieves timed gene activation by sequentially partnering with stage-specific transcription factors (TFs) in motor neuron (MN) differentiation. Genome-wide profiling revealed Kdm6b occupancy progressively shifted from proximal promoters to distal enhancers, along with increasing regulatory elements during maturation. At occupied sites, Kdm6b triggered rapid H3K27me3 loss with concurrent H3K27ac/H3K4me1 gain, establishing activation-competent chromatin. By integrating developmental TFs and histone modification landscapes, Kdm6b builds up the dynamic epigenetic choreography to precisely regulate MN developmental programs from early MN fate specification, intermediate cell differentiation and growth to later maturation. The ordered expression of developmental genes was compromised by stage-specific Kdm6b inhibition. Our work resolves how a single epigenetic regulator achieves temporal precision in driving stepwise MN development, with broad implications for neurodevelopment and diseases.

2025-09-24 | GSE305831 | GEO

Kdm6b-mediated epigenetic choreography of temporal precision during motor neuron differentiation

Project description:Kdm6b-mediated epigenetic choreography of temporal precision during motor neuron differentiation

| PRJNA1312061 | ENA

Stem cell-based approach to identify regulatory TFs during mammalian cell differentiation

Project description:Cell differentiation is controlled by transcription factors (TFs). However, we still do not fully understand which TFs are needed for even one mammalian differentiation pathway. To address this, we developed a detailed and integrated method. This method combines pluripotent stem cell differentiation in the lab, single-cell transcriptomics, and a CRISPR-based TF loss-of-function screen. Using this approach, we identified all the TFs required for spinal motor neuron (MN) differentiation in mice and their requirement in human MN differentiation. Our transcriptomic analysis revealed that while over 1,300 TFs are transcribed during ventral spinal cord differentiation, only 55 have annotated functions in the literature. The screen identified 232 TFs and other transcription-regulating genes essential for the progression of ventral spinal cord differentiation, including 116 TFs specifically required for MN differentiation. This approach led to three critical observations. First, the motor neuron progenitor (pMN) stage is a regulatory hub that correlates with a reduction in cell potential. Second, a secondary screen in human ventral spinal cord differentiation revealed a greater degree of conservation j between mouse pMNs and the human-specific ventral MN progenitors (vpMNs). This finding was unexpected, as the conservation was anticipated to be with the canonical human pMN stage. Third, the screen underscored the importance of the numerous and yet understudied ZF TFs controlling mammalian cell differentiation. In summary, we present a universal, unbiased strategy for studying TFs in mammalian differentiation, comparable to methodologies used in simpler organisms. This approach enhances our understanding of MN differentiation and provides a practical framework to identify all TFs required for any differentiation trajectory that can be recapitulated in vitro, offering many applications in various fields of developmental biology.

2025-09-01 | GSE285057 | GEO

Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [CutRun_CutTag]

Project description:Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [CutRun_CutTag]

| PRJNA1307991 | ENA

CRISPR-Cas9 combinatorial KO of epigenetic regulators in human ovarian cancer cells

Project description:We sequenced polyA mRNA from OVCAR8-ADR-Cas9 cells in which one or two of 3 epigenetic regulators (BRD4, KDM4C, KDM6B) had been knocked out to examine how global gene expression was affected and evaluate potential synergistic effects at a molecular level. Gene expression data (RNA-Seq) in OVCAR8-ADR-Cas9 cells infected with control vector or vectors expressing gRNAs targeting one of 4 epigenetic regulators (BRD4, KDM4C, KDM6B) with biological replicates.

2015-12-17 | E-GEOD-71074 | biostudies-arrayexpress

Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [RNA-seq]

Project description:Stage-specific Kdm6b-transcription factor partnerships orchestrate temporal precision during stepwise motor neuron differentiation [RNA-seq]

| PRJNA1307565 | ENA

Myeloid-specific KDM6B inhibition sensitizes Glioblastoma to PD1 blockade

Project description:Glioblastoma (GBM) tumors are enriched in immune-suppressive myeloid cells and are refractory to immune checkpoint therapy (ICT). Targeting epigenetic pathways to reprogram the functional phenotype of immune-suppressive myeloid cells to overcome resistance to ICT remains unexplored. Single-cell and spatial transcriptomic analyses of human GBM tumors demonstrated high expression of an epigenetic enzyme - histone 3 lysine 27 demethylase (KDM6B) in intra-tumoral immune-suppressive myeloid cell subsets. Importantly, myeloid-cell specific Kdm6b deletion enhanced pro-inflammatory pathways and improved survival in GBM tumor-bearing mice. Mechanistic studies elucidated that the absence of Kdm6b enhances antigen-presentation, interferon response and phagocytosis in myeloid cells by inhibiting mediators of immune suppression including Mafb, Socs3 and Sirpa. Further, pharmacological inhibition of KDM6B mirrored the functional phenotype of Kdm6b deleted myeloid cells and enhanced anti-PD1 efficacy. Thus, this study identified KDM6B as an epigenetic regulator of the functional phenotype of myeloid cell subsets and a potential therapeutic target to improve response to ICT.

| EGAS00001007002 | EGA

Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: RNA-seq

Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies. 3'end RNA sequencing

2014-04-14 | E-GEOD-54791 | biostudies-arrayexpress

Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: ChIP-seq

2014-04-10 | E-GEOD-54047 | biostudies-arrayexpress

Control of cell identity and early neural fate commitment by the enhancer module of Integrator

Project description:Lineage-specific transcription factors (TFs) operate as master orchestrators of developmental processes by activating select cis-regulatory enhancers and proximal promoters. Direct DNA binding of TFs ultimately drives context-specific recruitment of the basal transcriptional machinery that comprises RNA Polymerase II (RNAPII) and a host of polymerase-associated multiprotein complexes, including the metazoan-specific Integrator complex. Integrator is primarily known to modulate RNAPII processivity and to surveil RNA integrity across coding genes. Here we show an enhancer module of Integrator that directs cell fate specification by promoting epigenetic changes and TF binding at neural enhancers. Depletion of Integrator’s INTS10 upends neural traits and derails cells towards mesenchymal identity. Commissioning of neural enhancers relies on Integrator’s enhancer module, which stabilizes SOX2 binding at chromatin upon exit from pluripotency. We propose Integrator as a functional bridge between enhancers and promoters and a main driver of early development, providing new insight into a growing family of neurodevelopmental syndromes.

2024-08-15 | PXD054928 | Pride

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