Genome-wide maps of chromatin state during cardiac reprogramming of human fibroblasts by small molecules
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE78096 | GEO | 2016/02/19
SECONDARY ACCESSION(S): PRJNA312598
REPOSITORIES: GEO
Similar Datasets
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: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
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.
2014-03-13 | GSE55820 | 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: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: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: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. This SuperSeries is composed of the following subset Series: GSE14411: Gene expression in b1-integrin wild-type and knockout mouse heart GSE14412: Gene expression in mouse embyonic cardiomyocytes, fibroblasts and adult cardiac fibroblasts Refer to individual Series
2009-01-14 | E-GEOD-14414 | biostudies-arrayexpress
Project description:Fibroblasts can be reprogrammed into cardiomyocyte-like cells by overexpressing transcription factors, GATA4, Hand2, Mef2C and Tbx5 (GHMT). A83-01, an inhibitor of ALK4, ALK5 and ALK7 and two microRNA, miR-1 and miR-133 increase the efficiency of cardiac reprogramming. RNA_Seq was performed to anyalyze effects of these factors on gene expression. Total RNAs were prepared from mouse embryonic fibroblasts (MEFs); Reprogramming fibroblasts including MEFs transduced with retroviruses encoding GHMT, MEFs transduced with with retroviruses encoding GHMT plus miR-1 and miR-133 (GHMT2m), MEFs transduced with with retroviruses encoding GHMT2m treated with A83-01, at day 7 after viral transduction; and neonatal mouse cardiomyocytes (NMCMs).
2015-07-28 | E-GEOD-71405 | biostudies-arrayexpress
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 conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persists for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods. Mouse embryonic fibroblasts were treated with different combinations of transcription factors to drive transdifferentiation to induced cardiomyocytes (iCMs). Putative iCMs were enriched by zeocin selection. Zeocin resistance was conferred to iCMs via the TroponinT-GCaMP5-Zeo lentiviral reporter.
2013-04-22 | E-GEOD-45274 | biostudies-arrayexpress