Epigenetic Modifications of Stem Cells

Abstract

Stem cells of all types are characterized by the ability to self-renew and to differentiate. Multiple lines of evidence suggest that both maintenance of stemness and lineage commitment, including determination of the cardiomyogenic lineage, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications, and ATP-dependent chromatin remodeling. Epigenetic mechanisms are intrinsically reversible, interdependent, and highly dynamic in regulation of chromatin structure and specific gene transcription programs, thereby contributing to stem cell homeostasis. Here, we review the current understanding of epigenetic mechanisms involved in regulation of stem cell self-renewal and differentiation and in the control of cardiac progenitor cell commitment during heart development. Further progress in this area will help to decipher the epigenetic landscape in stem and progenitor cells and facilitate manipulation of stem cells for regenerative applications.

Disruption of spatiotemporal hypoxic signaling causes congenital heart disease in mice

“…CPCs of the FHF generate the left ventricle (LV) and parts of the inflow tract, while the right ventricle (RV), the atria, the outflow tract, and parts of the inflow tract are mainly derived from CPCs of the SHF (14,15). The transcription factors NK2 homeobox 5 (Nkx2.5) and islet 1 (ISL1) play key roles in the complex network, which controls fate decisions and expansion of CPCs (16)(17)(18). Isl1 expression marks cells in the SHF with a trilineage potential (cardiomyocytes, endothelial cells, and smooth muscle cells), but Isl1 is also expressed broadly in the coelomic mesoderm, which harbors precursors of both FHF and SHF (19).…”

Intrinsically Disordered Proteins: Controlled Chaos or Random Walk

“…Therefore, the uniqueness of each cell is derived not by the DNA sequence but instead by the availability of portions of the DNA within that particular cell. 34 The accessibility of genes is regulated not only through the prevalence of transcription factors and enhancers, but also through the structure of the DNA itself. The DNA of eukaryotes is associated with histone octamers that sequester approximately147 base pairs of DNA in a nucleosome complex.…”

Recent Developments in Cardiovascular Genetics

“…Regardless of their contributions to missing heritability or the lack thereof, epigenetic factors, whether through DNA methylation or through histone modifications of the chromatin, regulate various cardiovascular phenotypes, including development, 49 cardiac reprogramming, [50][51][52] angiogenesis and vascular functions, 51,53-57 myocardial repair, 58 and others. 49,56,59,60 Unlike the first 2 categories, the genomic biology is a rapidly evolving field and is likely to continue to expand in the coming years.…”