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TMEM88 knockdown during human embryonic stem cell cardiac differentiation

ABSTRACT: 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

ORGANISM(S): Homo sapiens

SUBMITTER: Nathan Palpant

PROVIDER: E-GEOD-43805 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transmembrane protein 88: a Wnt regulatory protein that specifies cardiomyocyte development.

Palpant Nathan J NJ Pabon Lil L Rabinowitz Jeremy S JS Hadland Brandon K BK Stoick-Cooper Cristi L CL Paige Sharon L SL Bernstein Irwin D ID Moon Randall T RT Murry Charles E CE

Development (Cambridge, England) 20130807 18

Genetic regulation of the cell fate transition from lateral plate mesoderm to the specification of cardiomyocytes requires suppression of Wnt/β-catenin signaling, but the mechanism for this is not well understood. By analyzing gene expression and chromatin dynamics during directed differentiation of human embryonic stem cells (hESCs), we identified a suppressor of Wnt/β-catenin signaling, transmembrane protein 88 (TMEM88), as a potential regulator of cardiovascular progenitor cell (CVP) specific ...[more]

PMID: 23924634

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TMEM88 knockdown during human embryonic stem cell cardiac differentiation

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.

2013-10-21 | GSE43805 | GEO

Human induced pluripotent stem cells: diploid, chr7q deletion, spontaneous chr7 correction

Project description:Gene expression analysis, a) comparing isogenic karyotypically normal iPSCs to del7q-iPSCs, b) comparing del7q-iPSCs to spontaneously corrected iPSCs. The chr7q deletion results in reduced expression levels of a large number of genes in the chr7q deleted region Two-condition experiment, del7q-iPSCs vs. isogenic normal iPSCs and del7q-iPSCs vs spontaneously corrected-iPSCs. Biological replicates: 3 control replicates, 3 del7q-iPSC replicates and 3 spontaneously corrected-iPSC replicates

2015-02-16 | E-GEOD-65215 | biostudies-arrayexpress

Sox7 regulates lineage decisions in cardiovascular progenitor cells

Project description:Specification of the mesodermal lineages requires a complex set of morphogenetic events orchestrated by interconnected signaling pathways and gene regulatory networks. The transcription factor Sox7 has critical functions in differentiation of multiple mesodermal lineages, including cardiac, endothelial, and hematopoietic. Using a doxycycline-inducible mouse embryonic stem cell (mESC) line, we have previously shown that expression of Sox7 in cardiovascular progenitor cells promotes expansion of endothelial progenitor cells. Here, we show that the ability of Sox7 to promote endothelial cell fate occurs at the expense of the cardiac lineage. Using ChIP-Seq coupled with ATAC-Seq we identify downstream target genes of Sox7 in cardiovascular progenitor cells and, by integrating these data with transcriptomic analyses, we define Sox7-dependent gene programs specific to cardiac and endothelial progenitor cells. Further, we demonstrate a protein-protein interaction between SOX7 and GATA4 and provide evidence that Sox7 interferes with the transcriptional activity of Gata4 on cardiac genes. In addition, we show Sox7 modulates WNT and BMP signaling during cardiovascular differentiation. Our data represent the first genome-wide analysis of Sox7 function and reveal a critical role for Sox7 in regulating signaling pathways that affect cardiovascular progenitor cell differentiation.

2019-07-06 | GSE133899 | GEO

Sox7 regulates lineage decisions in cardiovascular progenitor cells

Project description:Sox7 regulates lineage decisions in cardiovascular progenitor cells

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Real-time quantitative PCR analysis of microRNA expression in neonatal and adult cardiovascular progenitors

Project description:Human cardiovascular stem cells were isolated from adult (57-75 year old) and neonatal (<1 month old) atrial tissue. Cardiovascular stem cells were then cloned by single cell dilution and compared using sabiosciences cell development & differentiation miRNA PCR array. microRNA expression profiling by RT-PCR, 3 cardiac progenitor cell clones isolated from adults were run separately and results were pooled and compared to 8 neonatal cardiovascular progenitor cell clones that were run separately and pooled.

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Early Multipotent Cardiovascular Progenitors Derived from Pluripotent Stem Cells Engraft in Postmyocard Infarted Primate

Project description:During embryogenesis, the cardiac cell fate is acquired as early as gastrulation. There is compelling evidence that embryonic stem cells (ESC) can recapitulate early steps in cardiogenesis. Identification from human pluripotent stem cells of early cardiovascular cell progenitors, at the origin of the first cardiac lineage, would shed light on human normal and pathological cardiogenesis and would pave the way toward cell therapy for cardiac degenerative diseases. Here, we report the isolation, and a phenotypic characterisation of an early Oct-4+, SSEA-1+, Mesp1+ population of cardiovascular progenitors derived from human pluripotent stem cells. This multipotential progenitor features the capability to generate cardiomyocytes as well as smooth muscle and endothelial cells. We further bring a proof of concept that these progenitors can be used in cardiac regenerative medicine as allografted in infarcted non human primate myocardium, they differentiate in ventricular myocytes without any adverse effect. One RNA sample from HUESC-POU5F1 was compared in dye-swap to undifferentiated HUESC. Three distinct RNA samples from BMP2-induced SSEA1+ cells were compared in dye-swap to paired remaining SSEA1-. Reference samples correspond to undifferentiated HUESC and to SSEA1 negative cells, respectively. population respectivement.

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Early lineage restriction and regional segregation during mammalian heart development

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2014-07-10 | E-GEOD-59033 | biostudies-arrayexpress

Notch Activation Commits Mesoderm Cells to the Cardiac Lineage [cardiomyocytes]

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.

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Notch Activation Commits Mesoderm Cells to the Cardiac Lineage [embryo]

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