Cell Reprogramming experiment (reprogramming cardiac fibroblasts into cardiomyocytes)
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ABSTRACT:
PROVIDER: PRJNA213262 | ENA |
REPOSITORIES: ENA
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Project description:Cells were reprogrammed from cardiac fibroblasts to cardiomyocytes, in various conditions. These are the iCM cells (induced cardiomyocytes). There are both human and mouse arrays here, as seen below. Microarrays were used to measure the overall degree to which cellular repogramming was successful, by comparing the reprogrammed cells to reference populations of cardiomyocytes (CMs) and cardiac fibroblasts (CFs).
2013-07-26 | E-GEOD-49192 | biostudies-arrayexpress
Project description:Cells were reprogrammed from cardiac fibroblasts to cardiomyocytes, in various conditions. These are the iCM cells (induced cardiomyocytes). There are both human and mouse arrays here, as seen below.
2013-07-26 | GSE49192 | GEO
Project description:The reprogramming of fibroblast cells to induced pluripotent stem (iPS) cells raises the possibility that a somatic cell could be reprogrammed to an alternative differentiated fate without first becoming a stem/progenitor cell. A large pool of fibroblast cells exists in the post-natal heart, yet no single “master regulator” of direct cardiac reprogramming has been identified. Here, we report that a combination of three developmental transcription factors (i.e., Gata4, Mef2c and Tbx5) rapidly and efficiently reprogrammed post-natal cardiac or tail-tip fibroblasts directly into differentiated cardiomyocyte-like cells. Induced cardiomyocytes expressed cardiac-specific markers, had a global gene expression profile similar to cardiomyocytes, and contracted spontaneously. Fibroblast cells transplanted into mouse hearts one day after transduction of the three factors also differentiated into cardiomyocyte-like cells. These findings demonstrate that functional cardiomyocytes can be directly reprogrammed from differentiated somatic cells by defined factors. Reprogramming of endogenous or explanted fibroblast cells might provide a source of cardiomyocytes for regenerative approaches.
2010-06-12 | GSE22292 | GEO
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation. To identify candidate fibroblast-derived factors that promote myocyte proliferation, we isolated RNA from Nkx-YFP+ cardiomyocytes, embryonic cardiac fibroblasts, and adult cardiac fibroblasts and profiled mRNA expressions by microarray analyses. Arrays were performed using Affymetrix mouse Gene 1.0 ST arrays. Analysis was performed on three biological replicates of mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts.
2009-01-14 | E-GEOD-14412 | biostudies-arrayexpress
Project description:Conversion of fibroblasts to functional cardiomyocytes represents a potential approach for restoring cardiac function following myocardial injury, but the technique thus far has been slow and inefficient. To improve the efficiency of reprogramming fibroblasts to cardiac-like myocytes (iCMs) by cardiac transcription factors (Gata4, Hand2, Mef2c, and Tbx5=GHMT), we screened 192 protein kinases and discovered that Akt/protein kinase B dramatically accelerates and amplifies this process. Approximately 50% of reprogrammed fibroblasts displayed spontaneous beating after three weeks of induction by Akt plus GHMT. Furthermore, addition of Akt1 to GHMT evoked a more mature cardiac phenotype for iCMs, as seen by enhanced polynucleation, cellular hypertrophy, gene expression, and metabolic reprogramming. Igf1 and Pi3 kinase acted upstream of Akt, whereas mTORC1 and Foxo3a acted downstream of Akt to influence fibroblast-to-cardiomyocyte reprogramming. These findings provide new insights into the molecular basis of cardiac reprogramming and represent an important step toward further application of this technique.
2015-10-01 | GSE68509 | GEO
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
Project description:Direct cardiac reprogramming converts fibroblasts into induced cardiomyocytes (iCMs) with the minimal combination of transcription factors, Gata4 (G), Mef2c (M), and Tbx5 (T). However, the induction of functional mature iCMs is inefficient and the mechanisms remain elusive. Mef2c is a central transcription factor in direct cardiac reprogramming. We investigated the effect of Mef2c isoforms(M1, M2, M6) and transcriptional activity (M2TAD) on cardiac reprogramming on cardiac reprogramming. Then, we found that the active form of Mef2c evoked epigenetic remodeling cooperating with p300 and promoted the maturation of iCMs.
2023-06-13 | GSE196293 | GEO
Project description:During reprogramming of fibroblasts into cardiomyocyte-like cells by overexpression of transcription factors, GATA4, Hand2, Mef2C and Tbx5 (GHMT), H3K4Me2, an active histone code, shifts from fibroblast-exclusive peaks to cardiomyocyte-exclusive peaks. Important cardiac genes are gradually marked by this active histone marker. Mouse embryonic fibroblasts (MEFs) and neonatal mouse ventricular cardiomyocytes (NMVMs) represent fibroblasts and cardiomyocytes, respectively. Chromatins harvested from MEFs infected with retroviruses carrying GHMT at day 3, day 5, day 7 post-viral infection were prepared for immunoprecipitation.
2015-07-28 | E-GEOD-71392 | biostudies-arrayexpress
Project description:Direct cardiac reprogramming to induce cardiomyocyte-like cells, e.g. by GMT (Gata4, Mef2c and Tbx5), is a promising route for regenerating damaged heart in vivo and disease modeling in vitro. Supplementation with additional factors and chemical agents can enhance efficiency but raises concerns regarding selectivity to cardiac fibroblasts and complicates delivery for in situ cardiac reprogramming. Here, we screened 2000 chemicals with known biological activities and found that a combination of 2C (SB431542 and Baricitinib) significantly enhances cardiac reprogramming by GMT. Without Gata4, MT (Mef2c and Tbx5) plus 2C could selectively reprogram cardiac fibroblasts with enhanced efficiency, kinetics and cardiomyocyte function. More importantly, 2C+MYOCD selectively reprograms human cardiac fibroblasts into cardiomyocyte-like cells. 2C enhances cardiac reprogramming by inhibiting Alk5, Tyk2 and downregulating Oas2, Oas3, Serpina3n and Tgfbi. 2C thus enables selective and robust cardiac reprogramming that can greatly facilitate disease modeling in vitro and advance clinical therapeutic heart regeneration in vivo.
2023-12-13 | GSE213021 | GEO
Project description:Growth and expansion of ventricular chambers is essential during cardiogenesis and is achieved by proliferation of cardiac progenitors that are not fully differentiated. Disruption of this process can lead to prenatal lethality. In contrast, adult cardiomyocytes achieve growth through hypertrophy rather than hyperplasia. Although epicardial-derived signals may contribute to the proliferative process in myocytes, the factors and cell types responsible for development of the ventricular myocardial thickness are unclear. Moreover, the function of embryonic cardiac fibroblasts, derived from epicardium, and their secreted factors are largely unknown. Using a novel co-culture system, we found that embryonic cardiac fibroblasts induced proliferation of cardiomyocytes, in contrast to adult cardiac fibroblasts that promoted myocyte hypertrophy. We identified fibronectin, collagen and heparin-binding EGF-like growth factor as embryonic cardiac fibroblast-specific signals that collaboratively promoted cardiomyocyte proliferation in a paracrine fashion. b1 integrin was required for this proliferative response, and ventricular cardiomyocyte-specific deletion of b1 integrin in mice resulted in reduced myocardial proliferation and impaired ventricular compaction. These findings reveal a previously unrecognized paracrine function of embryonic cardiac fibroblasts in regulating cardiomyocyte proliferation.
2009-01-15 | GSE14412 | GEO