Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells
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ABSTRACT:
PROVIDER: PRJNA639801 | ENA |
REPOSITORIES: ENA
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Project description:Here we established a differentiation strategy that promotes the specification, proliferation and maturation of a compact cardiomyocyte population from hPSCs. The cardiomyocytes generated under these conditions display the hallmark phenotypic characteristics of post-natal cardiomyocytes.
2020-06-17 | GSE152589 | GEO
Project description:The generation of sufficient numbers of mature ventricular myocytes for effective cell-based therapy is a central barrier for cardiac regenerative medicine. Here we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes, and consistent with other reports of iPSCs derived from various somatic cell types, ventricular myocyte derived iPSCs (ViPSCs) exhibit a markedly higher propensity to differentiate into beating cardiomyocytes as compared to genetically-matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, ViPSC-derived cardiomyocytes form up to 99% ventricular myocytes suggesting that ventricular myocyte-derived iPSCs may be a viable strategy to generate specific cardiomyocyte subtypes for cell-based therapies. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the ventricular myocyte fate in pluripotent stem cells. Total RNA was extracted from mouse ES cells, tail tip fibroblasts (TTFs), ventricular myocytes (VMs), TTF-derived induced pluripotent stem cells (TiPSCs) and VM-derived induced pluripotent stem cells (ViPSCs). Global gene expression profiling was performed using affymetrix mouse 430 2.0 gene arrays.
2011-10-04 | E-GEOD-32598 | biostudies-arrayexpress
Project description:The generation of sufficient numbers of mature ventricular myocytes for effective cell-based therapy is a central barrier for cardiac regenerative medicine. Here we demonstrate that induced pluripotent stem cells (iPSCs) can be derived from murine ventricular myocytes, and consistent with other reports of iPSCs derived from various somatic cell types, ventricular myocyte derived iPSCs (ViPSCs) exhibit a markedly higher propensity to differentiate into beating cardiomyocytes as compared to genetically-matched embryonic stem cells (ESCs) or iPSCs derived from tail-tip fibroblasts. Strikingly, ViPSC-derived cardiomyocytes form up to 99% ventricular myocytes suggesting that ventricular myocyte-derived iPSCs may be a viable strategy to generate specific cardiomyocyte subtypes for cell-based therapies. The enhanced ventricular myogenesis in ViPSCs is mediated via increased numbers of cardiovascular progenitors at early stages of differentiation. In order to investigate the mechanism of enhanced ventricular myogenesis from ViPSCs, we performed global gene expression and DNA methylation analysis, which revealed a distinct epigenetic signature that may be involved in specifying the ventricular myocyte fate in pluripotent stem cells.
2011-10-05 | GSE32598 | GEO
Project description:Adult ventricular cardiomyocytes
| PRJNA556434 | ENA
Project description:Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.
| S-EPMC8155185 | biostudies-literature
Project description:Profiling global gene expression of undifferentiated human embryonic stem cells, artificially derived cardiomyocytes, fetal ventricular cardiomyocytes, and adult ventricular cardiomyocytes to determine transcriptomic variation between these cell types. Total RNA extracted from 10 human samples representing four stages of cardiac development from undifferentiated stem cells to mature adult cardiac tissue.
2013-09-10 | E-GEOD-50704 | biostudies-arrayexpress
Project description:We addressed the question of which protein kinases are expressed in cardiomyocytes. We assessed the changes during postnatal development, comparing profiles in rat neonatal ventricular cardiomyocytes (NVMs) with adult ventricular cardiomyocytes (AVMs). Neonatal and adult rat ventricular cardiomyocytes prepared according to established procedures (Marshall et al. PLoS ONE 2010 5(4):e10027; Fuller and Sugden, FEBs Lett. 1989 247:209-12; Rodrigues and Severson In Biochemical Techniques in the Heart (McNeill, J. H., Ed.) pp 101-115, CRC Press, New York.). mRNA expression profiles compared using Affymetrix rat genome 230 2.0 arrays.
2015-01-01 | E-MTAB-2832 | biostudies-arrayexpress
Project description:The generation and purification of cardiomyocyte sub-population are critical for precise modelling of cardiac diseases, drug screening, and regenerative medicine due to their distinct phenotypic and functional characteristics. Therefore, identifying surface markers for cardiomyocyte subtypes that facilitate live cell sorting of homogenous population of cardiomyocytes is of utmost importance for successful translation of cardiovascular research and therapeutic applications. Using MARIS method coupled with RNA sequencing analysis on MLC2A- and MLC2V-expressing cardiomyocytes, we identified JAK2 as a potential cell surface marker for purifying ventricular cardiomyocytes. We demonstrated that that SIRPA+/JAK2+ population sorted expressed high levels of ventricular-specific marker and had electrophysiological properties that corresponded to ventricular-like cardiomyocytes. Functionally, SIRPA+/JAK2+ cardiomyocytes do not response to vernakalant, an atrial-selective anti-arrhythmic agent, confirming their identity as ventricular-like cells.
2023-12-01 | GSE231913 | GEO
Project description:Current differentiation protocols for human pluripotent stem cells produce a heterogeneous population of cardiomyocytes (CMs). Here, we identified CD151 as a marker of ventricular CMs (VCMs) and atrial CMs (ACMs) from 212 different cell surface markers. In the VCM induction, CD151high CMs were a homogeneous population of mature VCMs, including binuclear VCMs, and showed enriched cell cycle-related genes based on RNA-seq analysis. As for the ACM induction, CD151low CMs expressed high levels of atrial-related genes and exhibited atrial-type electrophysiological properties. According to RNA-seq analysis, CD151high CMs from the ACM induction had molecular signatures for cell-cell interactions and NOTCH signaling. When treated with a NOTCH signal inhibitor, the same cells showed mature electrophysiological properties consistent of ACMs with an increasing expression of atrial-related genes. Altogether, we found that CD151 is an indicator of subtype specification with distinct mechanisms between VCM and ACM differentiation and that NOTCH signaling inhibition enhances atrial specification.
2024-01-29 | GSE179769 | GEO
Project description:Study on changes in gene expression in primary cultures of neonatal rat ventricular cardiomyocytes to electric stimulation. Through comparing non-stimulated, stimulated and blebbistatin supplemented and stimulated cultures we set out to identify the genes that are specifically activated by electric pulsing separate from cardiomyocyte contractions. After initial recovery phase, primary cultures of neonatal rat ventricular cardiomyocytes were cultured for 3 days without pulsing, with electric pulsing or with electric pulsing combined with blebbistatin. Per treatment: 3 arrays, with samples obtained from 3 separate series of cardiomyocyte isolation and culturing. Per array: sample prepared from pooled (1:1) RNA from duplicate experiments.
2009-12-10 | E-GEOD-15856 | biostudies-arrayexpress