Single-cell RNA-seq of Mesp1+ mesoderm from ES cells
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ABSTRACT:
PROVIDER: PRJNA512079 | ENA |
REPOSITORIES: ENA
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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
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.
2016-01-12 | GSE74682 | GEO
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
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
Project description:Mesp1 is a transcription factor that promotes differentiation of pluripotent cells into different mesoderm lineages including hematopoietic, cardiac and skeletal myogenic. This occurs via at least two transient cell populations: a common hematopoietic/cardiac progenitor population and a common cardiac/skeletal myogenic progenitor population. It is not established whether Mesp1-induced mesoderm cells are intrinsically heterogeneous, or are simply capable of multiple lineage decisions. In the current study, we applied single-cell RNA-seq to analyze Mesp1+ mesoderm. Initial whole transcriptome analysis showed a surprising homogeneity among Mesp1-induced mesoderm cells. However, this apparent global homogeneity masked an intrinsic heterogeneity revealed by interrogating a panel of early mesoderm patterning factors. This approach enabled discovery of subpopulations primed for hematopoietic or cardiac development. These studies demonstrate the heterogeneic nature of Mesp1+ mesoderm.
| S-EPMC4873396 | biostudies-literature
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
Project description:Previously, we reported that the transcription factor Mesp1 promotes the cell fates of cardiomyocytes, smooth muscle, and vascular endothelium. Recently, hematopoietic stem cells (HSCs) were shown to derive from hemogenic endothelium. Since Mesp1 regulates development of endothelium, it potentially could influence gene expression related to hematopoietic development. Our present fate mapping study found that Mesp1-cre efficiently labeled hematopoietic lineages in vivo. This result suggested that Mesp1 might be expressed in progenitors of the hematopoietic system, such as hemogenic endothelium. To test this, we purified Flk1+ Tie2+ endothelium derived from differentiating ES cells with or without Mesp1 induction, and used microarray expression analysis to identify genes strongly up-regulated by Mesp1.
2012-08-03 | GSE34537 | GEO
Project description:Previously, we reported that the transcription factor Mesp1 promotes the cell fates of cardiomyocytes, smooth muscle, and vascular endothelium. Recently, hematopoietic stem cells (HSCs) were shown to derive from hemogenic endothelium. Since Mesp1 regulates development of endothelium, it potentially could influence gene expression related to hematopoietic development. Our present fate mapping study found that Mesp1-cre efficiently labeled hematopoietic lineages in vivo. This result suggested that Mesp1 might be expressed in progenitors of the hematopoietic system, such as hemogenic endothelium. To test this, we purified Flk1+ Tie2+ endothelium derived from differentiating ES cells with or without Mesp1 induction, and used microarray expression analysis to identify genes strongly up-regulated by Mesp1. Embryonic stem (ES) cells harboring a doxycycline (dox)-inducible Mesp1 gene (A2lox.Mesp1) were differentiated as embryoid bodies for 5 days in the absence (-) or presence (+) of dox from day 2 to day 4. Flk1+Tie2+ endothelial cells were purified by cell sorting for RNA extraction and hybridization on Affymetrix microarrays.
2012-08-02 | E-GEOD-34537 | biostudies-arrayexpress
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
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