Progressive Chromatin Condensation and {H3K9} Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells

摘要

Summary Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization affects the lineage potential of stem cells and that manipulation of chromatin dynamics influences stem cell function. Using nuclease sensitivity assays, we found a progressive decrease in chromatin digestion among pluripotent embryonic stem cells (ESCs), multipotent hematopoietic stem cells (HSCs), and mature hematopoietic cells. Quantitative high-resolution microscopy revealed that {ESCs} contain significantly more euchromatin than HSCs, with a further reduction in mature cells. Increased cellular maturation also led to heterochromatin localization to the nuclear periphery. Functionally, prevention of heterochromatin formation by inhibition of the histone methyltransferase {G9A} resulted in delayed {HSC} differentiation. Our results demonstrate global chromatin rearrangements during stem cell differentiation and that heterochromatin formation by {H3K9} methylation regulates {HSC} differentiation.