Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Zbtb16 determines the fate plasticity of cardiovascular progenitors through IGF2BP3-mediated mRNA stabilization [scRNA-seq]

ABSTRACT: Cardiovascular progenitors (CPs) are responsible for generating the diverse cell populations in hearts, exhibiting significant transcriptional heterogeneity. However, the regulation of fate plasticity among heterogeneous CP subpopulations, as well as the intrinsic regulatory factors, remains poorly understood. In this study, we characterized three CP subpopulations derived from pluripotent stem cells and found that the deletion of ZBTB family protein Zbtb16 led to a profound imbalance in the branching transition trajectory of Early-CPs, redirecting them toward CPs committed to endothelial cells and cardiac fibroblasts (EC/CF-CPs) rather than that to cardiomyocytes (CM-CPs). Mechanistic studies revealed that Zbtb16 interacted with the m6A reader IGF2BP3 to post-transcriptionally recognize and stabilize the mRNAs of key genes critical for the CM-CP subpopulation determination. Collectively, our findings established Zbtb16 as a key regulator of fate plasticity of heterogeneous CP subpopulations and revealed the interplay with IGF2BP3 to impact the m6A-modified mRNA stabilization, which provided new insights into the intrinsic connections between CP subpopulation plasticity and cardiovascular multi-lineage fate determination.

ORGANISM(S): Mus musculus

PROVIDER: GSE279846 | GEO | 2025/08/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Zbtb16 determines the fate plasticity of cardiovascular progenitors through IGF2BP3-mediated mRNA stabilization [RIP-Seq]

Project description:Cardiovascular progenitors (CPs) are responsible for generating the diverse cell populations in hearts, exhibiting significant transcriptional heterogeneity. However, the regulation of fate plasticity among heterogeneous CP subpopulations, as well as the intrinsic regulatory factors, remains poorly understood. In this study, we characterized three CP subpopulations derived from pluripotent stem cells and found that the deletion of ZBTB family protein Zbtb16 led to a profound imbalance in the branching transition trajectory of Early-CPs, redirecting them toward CPs committed to endothelial cells and cardiac fibroblasts (EC/CF-CPs) rather than that to cardiomyocytes (CM-CPs). Mechanistic studies revealed that Zbtb16 interacted with the m6A reader IGF2BP3 to post-transcriptionally recognize and stabilize the mRNAs of key genes critical for the CM-CP subpopulation determination. Collectively, our findings established Zbtb16 as a key regulator of fate plasticity of heterogeneous CP subpopulations and revealed the interplay with IGF2BP3 to impact the m6A-modified mRNA stabilization, which provided new insights into the intrinsic connections between CP subpopulation plasticity and cardiovascular multi-lineage fate determination.

2025-08-08 | GSE279399 | GEO

Dynamic BAF chromatin remodeling complex subunit inclusion promotes temporally distinct gene expression programs in cardiogenesis

Project description:Chromatin remodeling complexes instruct cellular differentiation and lineage specific transcription. The BRG1/BRM associated factor (BAF) complexes are important for several aspects of differentiation. We show that the catalytic subunit Brg1 has a specific role in cardiac precursors (CPs) to initiate cardiac gene expression programs and repress non-cardiac expression. Using immunoprecipitation immunopurification with mass spectrometry we determined the dynamic composition of BAF complexes during mammalian cardiac differentiation, identifying several cell-type specific subunits. We focused on the CP- and cardiomyocytes (CM)-enriched subunits BAF60c (SMARCD3) and BAF170 (SMARCC2). Baf60c and Baf170 co-regulate gene expression with Brg1 in CPs, and in CMs their loss results in broadly deregulated cardiac gene expression. BRG1, BAF60, and BAF170 modulate chromatin accessibility, to either promote accessibility at activated genes, while closing up chromatin at repressed genes. BAF60c and BAF170 are required for proper BAF complex composition, and BAF170 loss leads to retention of BRG1 at CP-specific enhancers. Thus, dynamic interdependent BAF complex subunit assembly modulates chromatin states and thereby participates in directing temporal gene expression programs in cardiogenesis.

2019-11-13 | PXD012721 | Pride

Comparative Single Cell Transcriptomics Reveals Distinct Cell Fate Transition Statuses during Human Cardiac Reprogramming

Project description:Direct lineage conversion among various somatic cell types revolutionized the field of stem cell and regenerative medicine. In addition, the platform of cellular reprogramming offered a powerful system to gain new knowledge about cell plasticity and cell fate determination and ultimately challenged previous notions of cell identity. Previously, we successfully utilized single cell transcriptomics to reconstruct the molecular routes of how a murine fibroblast adopts cardiomyocyte fate following a continuum of states. In this study, we employed a comparative single cell transcriptomics approach to study human cardiac reprogramming. In comparison with murine fibroblasts and other human cell types, we identified unexpected heterogeneity in human cardiac fibroblasts that was mainly due to variance in cell cycle status. Trajectories inferred by SLICER suggest molecular routes and pathways taken by human fibroblasts when transiting into CM fate. Importantly, by assigning a “cell fate index” to each single cell on the iCM trajectories resolved from both mouse and human fibroblasts, we discovered species differences in fibroblast plasticity and intermediate cell fate statuses when reprogrammed towards a CM fate. Collectively, our comparative single cell transcriptomics study of human cardiac reprogramming revealed previously unrecognized molecular features of human cardiac fibroblasts and regulatory mechanisms in human cardiomyocyte cell fate control.

2019-06-20 | GSE106888 | GEO

Unravelling the chromatin landscape and enhancer logic mediating spatiotemporal patterning of early cardiovascular progenitors [RNA-seq]

Project description:The mammalian heart arises from various populations of Mesp1-expressing cardiovascular progenitors (CPs) that are specified during the early stages of gastrulation. Mesp1 acts as a master regulator of CP specification and differentiation. However, how Mesp1 regulates the chromatin landscape of nascent mesodermal cells to define the temporal and spatial patterning of the distinct populations of CP remains unknown. Here, by combining ChIP-seq, RNA-seq and ATAC-seq during mouse pluripotent stem cell differentiation, we defined the temporal remodelling of the chromatin landscape mediated by Mesp1. We identified different enhancers that are temporally regulated to erase the pluripotent state and specify the pools of CPs that mediate heart development. We found that Mesp1 acts as a pioneer transcription factor (TF) and identified Zic TFs as essential cofactors that regulate Mesp1 pioneer activity at key mesodermal enhancers, thereby regulating the chromatin remodelling and gene expression associated with the specification of the different populations of CPs in vivo. Our study identifies the dynamics of the chromatin landscape and enhancer remodelling associated with temporal patterning of early mesodermal cells into the distinct populations of CPs that mediate heart development.

2022-05-18 | GSE165103 | GEO

Unravelling the chromatin landscape and enhancer logic mediating spatiotemporal patterning of early cardiovascular progenitors [ATAC-seq]

2022-05-18 | GSE165101 | GEO

Unravelling the chromatin landscape and enhancer logic mediating spatiotemporal patterning of early cardiovascular progenitors [ChIP-seq]

2022-05-18 | GSE165102 | GEO

The origin and dynamics of cellular heterogeneity vary across lineage subtypes of castrate resistant prostate cancer [scRNA-seq]

Project description:Cancer cells often adapt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. We assessed the dynamics of lineage determination and cellular subpopulation expansion in treatment-resistant adenocarcinoma, amphicrine, and small cell neuroendocrine castrate resistant prostate cancers.

2023-07-24 | GSE237602 | GEO

The origin and dynamics of cellular heterogeneity vary across lineage subtypes of castrate resistant prostate cancer [scATAC-seq]

2023-07-24 | GSE237601 | GEO

Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis [Chip-Seq]

Project description:Genome-wide occupancy analysis of TBX5, NKX2-5 and GATA4 in differentiating WT, Nkx2-5KO (NKO), Tbx5KO (TKO) and Nkx2-5;Tbx5KO (DKO) cells at the cardiac precursor (CP) and cardiomyocyte (CM) differentiation stages. Analysis of TBX5, NKX2-5 and GATA4 occupancy a and gene expression in WT, Tbx5KO, Nkx2-5KO and DoubleKO precursor (CP) and mature (CM) in vitro differentiated cardiomyocytes.

2016-02-11 | GSE77548 | GEO

Single-cell molecular analysis defines therapy-response and immunophenotype of stem cell populations in CML

Project description:Understanding leukemia heterogeneity is critical for the development of curative treatments as the failure to eliminate therapy-persistent leukemic stem cells (LSCs) may result in disease relapse. Here we have combined high-throughput immunophenotypic screens with large-scale single-cell gene expression analysis to define the heterogeneity within the LSC-population in chronic phase (CP) chronic myeloid leukemia (CML) patients at diagnosis and following conventional tyrosine kinase inhibitor (TKI) treatment. Our results reveal substantial heterogeneity within the putative LSC population in CP-CML and demonstrate differences in response to subsequent TKI-treatment between distinct subpopulations. Importantly, LSC subpopulations with myeloid and proliferative molecular signatures are proportionally reduced at a higher extent in response to TKI-therapy compared to subfractions displaying primitive and quiescent signatures. Additionally, cell surface expression of the CP-CML stem cell markers CD25, CD26 and IL1RAP is high on all subpopulation at diagnosis, but downregulated and unevenly distributed across subpopulations in response to TKI-treatment. The most TKI-insensitive cells of the LSC-compartment can be captured within the CD45RA- fraction and further defined as positive for CD26 in combination with an aberrant lack of cKIT expression. Thus, our results reveal the heterogeneity of the CML stem cell population and propose a Lin-CD34+CD38-/lowCD45RA-cKIT-CD26+ population to be targeted for improved therapy response.

2017-01-27 | GSE84507 | 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