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

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

PROVIDER: PRJNA1091899 | ENA |

REPOSITORIES: ENA

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

Project description: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.

2024-03-31 | GSE262452 | 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

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

2016-01-12 | GSE74682 | 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

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

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

| PRJNA512079 | ENA

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

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

Next Generation Sequencing Analysis of human embryonic stem cells derived MESP1-mTomato reporter cells

Project description:Purpose: To compare the transcriptome of MESP1-mTomato reporter cells at undifferentiated state, mesoderm differentiation day 3 mTomato+ and mTomato- cells and MESP1+ cells undergoing endothelial differentiation in 2D and 3D. 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. Libraries 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.

2016-12-01 | GSE79470 | 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

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