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Gene expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes

ABSTRACT: Cardiomyocyte-like cells can be reprogrammed from somatic fibroblasts by combinations of genes, providing a new avenue for cardiac regenerative therapy. Here we show that functional cardiomyocytes can be rapidly and efficiently generated from human fibroblasts by specific combination small molecules. Microarray analysis has been used to compare the expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE55820 | GEO | 2014/03/13

SECONDARY ACCESSION(S): PRJNA241070

REPOSITORIES: GEO

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Gene expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes

Project description:Cardiomyocyte-like cells can be reprogrammed from somatic fibroblasts by combinations of genes, providing a new avenue for cardiac regenerative therapy. Here we show that functional cardiomyocytes can be rapidly and efficiently generated from human fibroblasts by specific combination small molecules. Microarray analysis has been used to compare the expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes. Cardiomyocytes generated from different origins were metabolically purified under glucose-depleted and lactate-abundant conditions for RNA extraction and hybridization on Affymetrix microarrays.

2014-03-13 | E-GEOD-55820 | biostudies-arrayexpress

Sensing Cardiac Electrical Activity with a Cardiomyocyte Targeted Optogenetic Voltage Indicator

Project description:Rationale: Monitoring and controlling cardiomyocyte activity with optogenetic tools offers exciting possibilities for fundamental and translational cardiovascular research. Genetically encoded voltage indicators may be particularly attractive for minimal invasive and repeated assessments of cardiac excitation from the cellular to the whole heart level. Objective: To test the hypothesis that cardiomyocyte-targeted voltage-sensitive fluorescence protein 2.3 (VSFP2.3) can be exploited as optogenetic tool for the monitoring of electrical activity in isolated cardiomyocytes and the whole heart as well as function and maturity in induced pluripotent stem cell (iPSC)-derived cardiomyocytes. Methods and Results: We first generated mice with cardiomyocyte-restricted expression of VSFP2.3 and demonstrated distinct sarcolemmal localization of VSFP2.3 without any signs for associated pathologies (assessed by echocardiography). Optically recorded VSFP2.3 signals correlated well with membrane voltage measured simultaneously by patch-clamping. The utility of VSFP2.3 for human action potential recordings was confirmed by simulation of immature and mature action potentials in murine VSFP2.3 cardiomyocytes. Optical cardiograms (OCGs) could be monitored in whole hearts ex vivo and minimally invasively in vivo via fiber optics at physiological heart rate (10 Hz) and under pacing-induced arrhythmia. Finally, we reprogrammed tail-tip fibroblasts from transgenic mice and used the VSFP2.3 sensor for benchmarking functional and structural maturation in iPSC-derived cardiomyocytes. Conclusions: We introduce a novel transgenic voltage-sensor model as a new method in cardiovascular research and provide proof-of-concept for its utility in optogenetic sensing of physiological and pathological excitation in mature and immature cardiomyocytes in vitro and in vivo. Determination of transgene (VSFP2.3) cardiotoxicity

2015-09-02 | E-GEOD-69190 | biostudies-arrayexpress

Single cell analysis of murine fibroblasts identifies neonatal to adult switching that regulates cardiomyocyte maturation

Project description:Cardiac maturation lays the foundation for postnatal heart development and disease, yet little is known about the contributions of the microenvironment to cardiomyocyte maturation. By integrating single-cell RNA-sequencing data of mouse hearts at multiple postnatal stages, we construct cellular interactomes and regulatory signaling networks. Here we report switching of fibroblast subtypes from a neonatal to adult state and this drives cardiomyocyte maturation. Molecular and functional maturation of neonatal mouse cardiomyocytes and human embryonic stem cell-derived cardiomyocytes are considerably enhanced upon coculture with corresponding adult cardiac fibroblasts. Further, single-cell analysis of in vivo and in vitro cardiomyocyte maturation trajectories identify highly conserved signaling pathways, pharmacological targeting of which substantially delays cardiomyocyte maturation in postnatal hearts, and markedly enhances cardiomyocyte proliferation and improves cardiac function in infarcted hearts. Together, we identify cardiac fibroblasts as a key constituent in the microenvironment promoting cardiomyocyte maturation, providing insights into how the manipulation of cardiomyocyte maturity may impact on disease development and regeneration.

2020-04-20 | GSE122706 | GEO

Transcriptome analysis of immediate early events in mRNA-mediated cellular reprogramming of human foreskin fibroblasts

Project description:In this study human neonatal foreskin fibroblasts (HFF1 and BJ) were lipofected with an equal mixture of human reprogramming factor-encoding mRNAs. The cells were lysed and total RNA was harvested 24 hours post-transfection. Gene regulation was evaluated with respect to corresponding mock-transfected, Lipofectamine-treated control fibroblasts. For comparison, wildtype (un-treated) HFF1 and BJ fibroblasts as well as undifferentiated HFF1- and BJ-derived induced pluripotent stem cells and human embryonic stem cells (generated and maintained in our laboratory (refer to GSE26575) were included in the analysis. Total RNA obtained from untreated human neonatal foreskin fibroblasts, reprogramming factor- and mock(Lipofectamine-treated)-transfected human neonatal fibroblasts, undifferentiated hESCs and iPSCs (derived from human neonatal foreskin fibroblasts).

2012-07-03 | E-GEOD-34943 | biostudies-arrayexpress

Isolated cardiomyocyte and cardiac fibroblast expression analysis

Project description:Some cell type-specific gene expression is maintained in the maturation of cardiomyocytes, where DNA hypomethylation of gene body regions of a set of specific genes. We used microarrays to detail the global gene expression program underlying the maintenance of cardiomyocyte function and maturation and compared it with DNA methylation status. Cardiomyocytes and cardiac fibroblasts were carefully isolated from neonatal and adult hearts and used fresh for the analysis.

2012-07-05 | E-GEOD-39039 | biostudies-arrayexpress

Genome-wide maps of chromatin state during cardiac reprogramming of human fibroblasts by small molecules

Project description:Cardiomyocyte-like cells can be reprogrammed from somatic fibroblasts by overexpression of cardiac genes, providing a new avenue for cardiac regenerative therapy. Here we report an alternative approach in which functional cardiomyocytes can be rapidly and efficiently generated from human fibroblasts by a specific combination of small molecules. ChIP-seq analysis has been used to understand the dynamic changes in chromatin state during early stage of reprogramming. We analyzed the genome-wide epigenetic changes by ChIP-seq analysis of H3K4me3 and H3K27ac (active chromatin marks) and H3K27me3 (inactive chromatin mark) at reprogramming Day 6 (D6) and day 11 (D11).

2016-02-19 | E-GEOD-78096 | biostudies-arrayexpress

Transcriptome data for human ES, FORESKIN and FORESKIN-derived iPS (ES4SKIN) cells

Project description:Assessing relevant differences between human induced pluripotent stem (iPS) cells and human embryonic stem (ES) cells is important, given that such differences may impact their potential therapeutic use. We used microarray to profile the changes in global gene expression arising from the reprogramming of somatic cells to induced pluripotent stem cells. Comparison of gene expression between human embryonic stem cells (HES-3), induced pluripotent stem cells (ES4SKIN) and its parental fibroblasts (FORESKIN). A pair of biololical replicates were analysed for each cell line.

2011-01-05 | E-GEOD-26451 | biostudies-arrayexpress

Genome-wide maps of chromatin state during cardiac reprogramming of human fibroblasts by small molecules

2016-02-19 | GSE78096 | GEO

Homo sapiens

Project description:Gene expression profile of cardiomyocyte-like cells derived from human foreskin and lung fibroblasts, and human ES cell-derived cardiomyocytes

| PRJNA241070 | ENA

Single-cell analysis of human iPSC-derived multi-lineage mini-cardiac organoid reveals molecular pathways to promote cardiomyocyte maturation and heart repair

Project description:Human induced pluripotent stem cell (hiPSC)-derived cardiovascular cells are promising cell source for cell therapy to repair the heart. Cardiac microtissue consisted of cardiomyocytes and fibroblast cells exhibited much better physiological functions. How different cardiovascular cell types interact and evolve in 3D microenvironment is unknown. In this study, we performed single-cell transcriptome profiling of hiPSC-derived mini-cardiac organoid consisted of cardiomyocytes, endothelial cells and smooth muscle cells. Our analysis showed that cardiac fibroblasts emerged spontaneously in 3D microenvironment which in turn facilitated the maturation of cardiomyocytes. HiPSC-derived cardiomyocytes, endothelial cells and smooth muscle cells assembled into mini-cardiac organoid in collagen-matrigel after 2 weeks. Single-cell study uncovered significant cell fate shift and improvement in cardiomyocyte maturation status upon-multilineage co-culture. Ligand-receptor analysis identified DLK1-Notch signaling to be one of the most upregulated pathways in the fibroblast population. Modulate the activity of DLK1-Notch signaling affected the assembly of the mini-cardiac organoid and the expression of immune regulatory genes. Interestingly, transplantation of trilineage mini-cardiac organoid into a rat model of myocardial infarction leads to significant improvement of cardiac function. Collectively, our single-cell analysis of mini-cardiac organoid provided rich information about cell fate dynamics and multilineage cross-talks occurred in the 3D microenvironment, which bring new insight on the molecular mechanism that promotes cardiomyocyte maturation and heart repair.

2023-02-09 | GSE166462 | GEO

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