Essential role of MESP1-RING1A complex in cardiac differentiation
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PROVIDER: PRJNA779988 | ENA |
REPOSITORIES: ENA
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Project description:Heart development is controlled by a complex transcriptional network composed of transcription factors and epigenetic regulators. Mutations in key developmental transcription factor MESP1, and chromatin factors such as PRC1 and cohesin components have been found in human congenital heart diseases (CHDs), although, their functional mechanism during heart development remains elusive. Here we find MESP1 interacts with RING1A/RING1, the core component of PRC1. RING1A depletion impairs human cardiomyocyte differentiation, and similar cardiac abnormalities were observed in Ring1A knockout mice as in patients with MESP1 mutations. Mechanistically, MESP1 associates with RING1A to activate cardiogenic genes through promoter-enhancer interactions mediated by cohesin and CTCF, and histone acetylation mediated by p300. Importantly, CHD mutations of MESP1 significantly affect such mechanisms and impair target gene activation. Together, our results demonstrate the importance of MESP1-RING1A complex in heart development and provide insights into pathogenic mechanisms of CHDs caused by mutations in MESP1, PRC1 and cohesin components.
2022-10-17 | GSE188721 | GEO
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
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:We explored the role of mammalian ETS1/2 and Mesp homologues of cardiogenic transcription factors of Ciona intestinalis, to convert primary human dermal fibroblasts into cardiac progenitors. ETS1/2 and Mesp homologues of cardiogenic transcription factors of Ciona intestinalis, to convert primary human dermal fibroblasts into cardiac progenitors. Here we show murine Ets2 has an obligatory role for directing cardiac progenitors during cardiopoesis in embryonic stem cells. ETS2 converted fibroblasts into KDR/Flk1+ replicative cells but, like the purported cardiac master regulatory gene Mesp1, could not by itself generate cardiac progenitors de novo from fibroblasts. Co-expression of both Ets2 and Mesp1, however, successfully reprogrammed differentiated fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, gap junction proteins, sarcomeric proteins, electrical activity and contractility. ETS2 and Mesp1 sit at the pinnacle of the cardiopoesis regulatory hierarchy and are well suited for treating human heart disease. Co-expression of both Ets2 and Mesp1, reprogrammed differentiated fibroblasts into cardiac progenitors All sample were done in triplicates, controls were NHDF and ETS2 only infected cells. NHDF were first infected with Doxycyline redulated (Doxy-) ETS2 lentivirus and supplemented with doxycycline for 1 week, sequentially cells were infected with Doxy-Mesp1 and treated for 1 more week. Cells were then aggegated to form EB and hangdrop for 1 week, at the end of that period cells were plated and samples were taken every 24 hrs
2012-06-30 | E-GEOD-29709 | biostudies-arrayexpress
Project description:We explored the role of mammalian ETS1/2 and Mesp homologues of cardiogenic transcription factors of Ciona intestinalis, to convert primary human dermal fibroblasts into cardiac progenitors. ETS1/2 and Mesp homologues of cardiogenic transcription factors of Ciona intestinalis, to convert primary human dermal fibroblasts into cardiac progenitors. Here we show murine Ets2 has an obligatory role for directing cardiac progenitors during cardiopoesis in embryonic stem cells. ETS2 converted fibroblasts into KDR/Flk1+ replicative cells but, like the purported cardiac master regulatory gene Mesp1, could not by itself generate cardiac progenitors de novo from fibroblasts. Co-expression of both Ets2 and Mesp1, however, successfully reprogrammed differentiated fibroblasts into cardiac progenitors, as shown by the de novo appearance of core cardiac transcription factors, gap junction proteins, sarcomeric proteins, electrical activity and contractility. ETS2 and Mesp1 sit at the pinnacle of the cardiopoesis regulatory hierarchy and are well suited for treating human heart disease. Co-expression of both Ets2 and Mesp1, reprogrammed differentiated fibroblasts into cardiac progenitors
2012-07-01 | GSE29709 | 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
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.
2016-01-01 | GSE73651 | GEO
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
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.
2014-09-01 | GSE56721 | GEO
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