TMEM88 knockdown during human embryonic stem cell cardiac differentiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE43805 | GEO | 2013/10/21
SECONDARY ACCESSION(S): PRJNA187477
REPOSITORIES: GEO
Similar Datasets
Project description:TMEM88 is indispensable for heart development and acts in the pre-cardiac mesoderm to specify lineage commitment of the cardiovascular progenitor cell through inhibition of Wnt signaling. 2 different lentiviruses expression shRNA targeting different domains of the TMEM88 locus were transduced into undifferentiated hES cells. Cells were puromycin selected then differentiated along the cardiac lineage. Total RNA was taken at day 5 of differentiation when the cardiovascular progenitor cell arises. 1 sample for each shRNA and 2 samples for control shRNA were analyzed by array
2013-10-21 | E-GEOD-43805 | biostudies-arrayexpress
Project description:Cardiac mesoderm, a precursor for all cardiovascular lineages, is a promising cell source for basic research and clinical applications. BMP/Nodal/Wnt signaling induces cardiac mesoderm in embryonic stem cells (ESCs); however the molecular mechanism is unclear and the differentiation protocols are labor-intensive. Identification of a master regulator that induces cardiac mesoderm is needed. Here we found that Tbx6 directly reprogrammed mouse fibroblasts into cardiac mesoderm-like cells, which differentiated into cardiomyocytes and smooth muscle cells with addition of lineage-specific transcription factors. In mouse ESCs, BMP/Activin (Nodal) induced Tbx6 in cardiac mesoderm, while inhibition of Tbx6 blocked differentiation into cardiac mesoderm and cardiomyocytes. Conversely, transient expression of Tbx6 induced cardiac mesoderm in ESCs without exogenous factors, and generated all cardiovascular lineages. Mechanistically, Tbx6 directly upregulated Mesp1, inhibited Sox2, and activated BMP/Nodal/Wnt signaling to induce cardiac mesoderm. Thus, Tbx6 acts as a key regulator for cardiac mesoderm induction, and our findings provide new insights into the mechanism of cardiovascular differentiation.
2018-10-19 | GSE89820 | GEO
Project description:Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1 establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.
2023-05-03 | GSE168580 | GEO
Project description:During early development multiple progenitor populations contribute to the formation of the four-chambered heart and its diverse lineages. However, the underlying mechanisms that result in the specification of these progenitor populations are not yet fully understood. We have recently identified a population of cells that gives rise selectively to cardiovascular cells of the heart ventricles. Here, we have used this knowledge to isolate and profile subsets of cardiac mesoderm cells from the mouse embryo and have identified an enrichment for the Notch signaling pathway in ventricular cardiac mesoderm. Using the pluripotent stem cell differentiation system to investigate the role of Notch in a temporally controlled manner, we show that Notch induction increases cardiomyocyte differentiation efficiency. This is due to the enhanced specification of mesoderm to the cardiac lineage. Finally, our data suggests that Notch interacts with WNT signaling to enhance commitment to the cardiac lineage. Overall, our findings support the notion that key signaling events during early heart development are critical for proper lineage specification and segregation and provide additional detail into these processes in mouse and human cardiogenesis.
2023-01-07 | GSE143226 | GEO
Project description:During early development multiple progenitor populations contribute to the formation of the four-chambered heart and its diverse lineages. However, the underlying mechanisms that result in the specification of these progenitor populations are not yet fully understood. We have recently identified a population of cells that gives rise selectively to cardiovascular cells of the heart ventricles. Here, we have used this knowledge to isolate and profile subsets of cardiac mesoderm cells from the mouse embryo and have identified an enrichment for the Notch signaling pathway in ventricular cardiac mesoderm. Using the pluripotent stem cell differentiation system to investigate the role of Notch in a temporally controlled manner, we show that Notch induction increases cardiomyocyte differentiation efficiency. This is due to the enhanced specification of mesoderm to the cardiac lineage. Finally, our data suggests that Notch interacts with WNT signaling to enhance commitment to the cardiac lineage. Overall, our findings support the notion that key signaling events during early heart development are critical for proper lineage specification and segregation and provide additional detail into these processes in mouse and human cardiogenesis.
2023-01-07 | GSE143227 | GEO
Project description:Self-organisation and coordinated morphogenesis of multiple cardiac lineages is essential for the development and function of the heart1-3. However, the absence of a human in vitro model that mimics the basic lineage architecture of the heart hinders research into developmental mechanisms and congenital defects4. Here, we describe the establishment of a reliable, lineage-controlled and high-throughput cardiac organoid platform. We show that cardiac mesoderm derived from human pluripotent stem cells robustly self-organises and differentiates into cardiomyocytes forming a cavity. Co-differentiation of cardiomyocytes and endothelial cells from cardiac mesoderm within these structures is required to form a separate endothelial layer. As in vivo, the epicardium engulfs these cardiac organoids, migrates into the cardiomyocyte layer and differentiates. We use this model to demonstrate that cardiac cavity formation is controlled by a mesodermal WNT-BMP signalling axis. Disruption of one of the key BMP targets in cardiac mesoderm, the transcription factor HAND1, interferes with cavity formation, which is consistent with its role in early heart tube and left chamber development5. Thus, the cardiac organoid platform represents a powerful resource for the quantitative and mechanistic analysis of early human cardiogenesis and defects that are otherwise inaccessible. Beyond understanding congenital heart disease, cardiac organoids provide a foundation for future translational research into human cardiac disorders.
2021-05-18 | PXD018306 | Pride
Project description:Purpose: Long non-coding RNAs (lncRNAs) display development-specific gene expression patterns, yet we know little about their precise roles in lineage commitment. Here, we discover a novel mammalian heart-associated lncRNA, AK143260, necessary for cardiac lineage specification. Methods: Gene expression profiles of mouse ESCs and differentiated organs were analyzed for master regulators of lineage commitment. The AK143260 transcript was shown to be strongly expressed in mESCs and in cells undergoing cardiac differentiation. Its role in cardiac differentiation was examined using depletion and in vitro differentiation systems, with morphological and gene expression profiling at different time-points. Results: mESCs depleted of AK143260, named Braveheart, fail to differentiate into cardiomyocytes and to activate a core cardiac gene regulatory network including key transcription factors driving cardiogenesis. We show that Braveheart functions upstream of MesP1 (mesoderm posterior 1), a transcription factor critical for specification of the earliest known multi-potent cardiovascular progenitor and in promoting epithelial-mesenchymal transition (EMT). Consistent with this, Braveheart depletion leads to morphological defects and loss of cardiogenic potential in a defined in vitro cardiomyocyte differentiation system. Furthermore, Braveheart is necessary to maintain myocardial gene expression and myofibril organization in neonatal cardiomyocytes. Conclusions: These findings reveal that Braveheart is an important regulator of cardiac commitment and implicate lncRNAs as potential therapeutic targets for cardiac disease and regeneration. Gene expression profiles from control and Bravheart-depleted mESCs were obtained by RNA-Seq on an Illumina HiSeq2000 instruments at Days 0,3,6 and 9. Gene expression profiles from mESCs, MEFs, partially reprogrammed MEFs and miPS cells were obtained by RNA-Seq on Illumina GAII/GAIIx instruments.
2013-01-30 | E-GEOD-39656 | biostudies-arrayexpress
Project description:Purpose: Long non-coding RNAs (lncRNAs) display development-specific gene expression patterns, yet we know little about their precise roles in lineage commitment. Here, we discover a novel mammalian heart-associated lncRNA, AK143260, necessary for cardiac lineage specification. Methods: Gene expression profiles of mouse ESCs and differentiated organs were analyzed for master regulators of lineage commitment. The AK143260 transcript was shown to be strongly expressed in mESCs and in cells undergoing cardiac differentiation. Its role in cardiac differentiation was examined using depletion and in vitro differentiation systems, with morphological and gene expression profiling at different time-points. Results: mESCs depleted of AK143260, named Braveheart, fail to differentiate into cardiomyocytes and to activate a core cardiac gene regulatory network including key transcription factors driving cardiogenesis. We show that Braveheart functions upstream of MesP1 (mesoderm posterior 1), a transcription factor critical for specification of the earliest known multi-potent cardiovascular progenitor and in promoting epithelial-mesenchymal transition (EMT). Consistent with this, Braveheart depletion leads to morphological defects and loss of cardiogenic potential in a defined in vitro cardiomyocyte differentiation system. Furthermore, Braveheart is necessary to maintain myocardial gene expression and myofibril organization in neonatal cardiomyocytes. Conclusions: These findings reveal that Braveheart is an important regulator of cardiac commitment and implicate lncRNAs as potential therapeutic targets for cardiac disease and regeneration.
2013-01-30 | GSE39656 | GEO
Project description:Exosomes were isolated from differentiating stem cells at various stages such as pluripotency, mesoderm, cardiac mesoderm, and cardiomyocytes. Proteomics were done on isolated exosomes.
2021-11-02 | PXD027888 | Pride
Project description:Mouse adult cardiac fibroblasts were infected with doxycycline inducible, 11 cardiac factors. Addition of doxycycline resulted in appearance of proliferative cells that had high nuclear-to-cytoplasmic ratio. We called these cells iCPCs. iCPC were stably reporgrammed and could be maintined in proliferative state without doxycycline. Here we compared the transcriptome of iCPC with their parental cells; adult cardiac fibroblasts. We found that iCPCs have upregulated genes involved in cardiovascular development and downregulated fibroblasts specific genes. iCPCs did not expressed endoderm, ectoderm or pluripotency associated genes indicating that they were cardiac mesoderm restricted progenitors. We isolated RNA from low passage iCPCs, high passage iCPCs and cardiac fibroblasts and performed RNASeq analysis
2015-09-16 | E-GEOD-61486 | biostudies-arrayexpress