Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

JAK Activity Regulates Mesoderm Cell Fate and Cardiac Differentiation by controlling MESP1 expression

ABSTRACT: Cardiac development requires precise gene expression programs at each developmental stage guided by multiple signaling pathways and transcription factors (TFs). MESP1 is transiently expressed in mesoderm, and is essential for subsequent cardiac development, while the precise mechanism regulating its own transcription and mesoderm cell fate is not fully understood. Therefore, we developed a high content screen assay to identify regulators of MESP1 expression in mesodermal cells differentiated from human pluripotent stem cells (hPSCs). The screen identified CYT387, a JAK1/JAK2 kinase inhibitor, as a potent molecule that can significantly increase MESP1 expression. CYT387 was also found to enhance cardiomyocyte differentiation from hPSCs in vitro. Mechanistical studies found that JAK inhibition promotes MESP1 expression by reducing cytoplasmic calcium concentration and subsequently activating canonical WNT signaling. Our study identified a role of JAK signaling in early mesoderm cells, and sheds light on the connection between the JAK-STAT pathway and transcriptional regulation of MESP1, which expands our understanding of mesoderm and cardiac development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE262452 | GEO | 2024/03/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene expression analysis of hESC-derived-MESP1 expressing progenitors

Project description:A hESC MESP1-MCHERRY reporter line was used to isolate and study the molecular character of MESP1 expressing pre-cardiac progenitors, derived from hESC. MESP1 is a key-transcription factor for pre-cardiac mesoderm and is marking the progenitor for almost all cells of the heart. This reporter line was used to study cardiac differentiation and the derivation of early cardiac progenitors in vitro. hESCs were differentiated towards the cardiac lineage, expressing MESP1-mCherry at day 3 of differentiation. Total RNA obtained from isolated MESP1-mCherry expressing progenitors was compared to that of non-MESP1-expressing progenitors and undifferentiated hESCs in order to characterize MESP1-specific transcription factors and proteins.

2014-09-01 | E-GEOD-56721 | biostudies-arrayexpress

Gene expression analysis of hESC-derived-MESP1 expressing progenitors

2014-09-01 | GSE56721 | GEO

Single-cell RNA-seq of Mesp1+ mesoderm from ES cells

Project description:We have developed a protocol to generate hematopoietic and cardiac derivatives in vitro by Mesp1 induction in ES cells. The goal of this study is to analyze the heterogeneity of Mesp1+ mesoderm by single-cell RNA-seq

2018-12-29 | GSE124454 | GEO

A Mesp1-dependent developmental breakpoint in transcriptional and epigenomic specification of early cardiac precursors

Project description:Transcriptional networks governing cardiac precursor cell (CPC) specification are incompletely understood due in part to limitations in distinguishing CPCs from non-cardiac mesoderm in early gastrulation. We leveraged detection of early cardiac lineage transgenes within a granular single cell transcriptomic time course of mouse embryos to identify emerging CPCs and describe their transcriptional profiles. Mesp1, a transiently-expressed mesodermal transcription factor (TF), is canonically described as an early regulator of cardiac specification. However, we observed perdurance of CPC transgene-expressing cells in Mesp1 mutants, albeit mis-localized, prompting us to investigate the scope of Mesp1’s role in CPC emergence and differentiation. Mesp1 mutant CPCs failed to robustly activate markers of cardiomyocyte maturity and critical cardiac TFs, yet they exhibited transcriptional profiles resembling cardiac mesoderm progressing towards cardiomyocyte fates. Single cell chromatin accessibility analysis defined a Mesp1-dependent developmental breakpoint in cardiac lineage progression at a shift from mesendoderm transcriptional networks to those necessary for cardiac patterning and morphogenesis. These results reveal Mesp1-independent aspects of early CPC specification and underscore a Mesp1-dependent regulatory landscape required for progression through cardiogenesis. This SuperSeries is composed of subseries.

2023-04-07 | GSE210639 | GEO

RNA-seq of Mesp1-induced cardiopharyngeal mesoderm derivatives from ES cells

Project description:We have developed a protocol to generate cardiopharyngeal mesoderm (CPM) in vitro by Mesp1 induction in ES cells. The goal of this study is to compare the transcriptome of CPM-derived cardiac and skeletal myogenic progenitors to identify novel lineage-specific markers. mRNA profiles of CPM-derived D6 (early) and D12 (late), cardiac (BMP) and skeletal myogenic (control) progenitors were generated

2016-01-12 | E-GEOD-74682 | biostudies-arrayexpress

RNA-seq of Mesp1-induced cardiopharyngeal mesoderm derivatives from ES cells

2016-01-12 | GSE74682 | GEO

Mesp1-induced gene expression changes

Project description:During gastrulation, cells of the prospective mesoderm ingress through the primitive streak and acquire fates based on complex spatial and temporal cues. Progenitors of the cardiogenic mesoderm are first found at E6.5 in the posterior lateral epiblast and subsequently migrate laterally and anteriorly to form the cardiac crescent at E7.5, when regionalized cell fates are first delineated . Lineage tracing and heterotopic transplantation studies suggest that precursors in the earliest heart field possess potential to generate myocardium, endocardium, and pericardium. The mechanisms by which inductive signals in the primitive streak effect the development of this pancardiac progenitor field, however, remain poorly understood In mice, the earliest restricted progenitors of the cardiovascular system are marked by expression of the basic helix-loop-helix transcription factor, Mesp1. We therefore use microarray analysis to determine the early and intermediate effects of transiently forced Mesp1 expression during ES cell differentiation. Keywords: time course

2008-07-01 | GSE5976 | GEO

Comprehensive gene expression analysis of a MESP1-progenitor derived cardiac lineage

Project description:A hESC MESP1 reporter line was used to isolate MESP1 expressing pre-cardiac progenitors. These progenitor were replated and fulter differentiated in culture. At four sequential timepoints upon further differentiation, samples were isolated for gene expression analysis, in order to identify key cardiac transcription factors and molecules. hESCs were differentiated towards the cardiac lineage. MESP1-mCherry expressing progenitors were isolated at day 3 of differentiation and replated as aggregates, in presence of Wnt-inhibitor Xav939. Two days after replating (D5), four days (D7), seven days (D10), ad 11 days (D14), total RNA of each sample was isolated for gene expression analysis. MESP1-mCherry positive derivatives were compared to MESP1-mCherry negative derivatives, in order to identify cardiac-specific regulators and cell surface markers.

2016-07-03 | E-GEOD-73651 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of mesoderm posterior bHLH transcription factor 1(MESP1)+ and MESP1- cells' Transcriptomes

Project description:Purpose: To compare the transcriptome of MESP1-mTomato reporter cells at undifferentiated state, cardiac differentiation day 3 and day 5. Methods: total RNA from sorted MESP1+, MESP1- and HESCs (in biological duplicates) was extracted using RNeasy Plus Mini Kit (Qiagen) and treated with RNase free DNase. RNA library was prepared following the instruction of TruSeq™ RNA Sample Preparation kit (Illumina) and sequenced on Illumina HiSeq 2000. Results: genes differentially expressed in MESP1-mTomato+ and mTomato- cells were identified. Conclusions: the gene expression profile of MESP1-mTomato cells indicates that they are cardiovascular progenitor cells.

2018-09-09 | GSE72862 | GEO

Transcription profiling of mouse ES cells bearing a targeted, doxycycline inducible Mesp1 transgene were differentiated in the absence or presence of DKK1

Project description:During gastrulation, cells of the prospective mesoderm ingress through the primitive streak and acquire fates based on complex spatial and temporal cues. Progenitors of the cardiogenic mesoderm are first found at E6.5 in the posterior lateral epiblast and subsequently migrate laterally and anteriorly to form the cardiac crescent at E7.5, when regionalized cell fates are first delineated . Lineage tracing and heterotopic transplantation studies suggest that precursors in the earliest heart field possess potential to generate myocardium, endocardium, and pericardium. The mechanisms by which inductive signals in the primitive streak effect the development of this pancardiac progenitor field, however, remain poorly understood; In mice, the earliest restricted progenitors of the cardiovascular system are marked by expression of the basic helix-loop-helix transcription factor, Mesp1. We therefore use microarray analysis to determine the early and intermediate effects of transiently forced Mesp1 expression during ES cell differentiation. Experiment Overall Design: ES cells bearing a targeted, doxycycline inducible Mesp1 transgene were differentiated in the absence or presence of DKK1 from day 0-4, either with or without transient doxycycline treatment from day 2-4.

2008-10-18 | E-GEOD-5976 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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