Successful differentiation of embryonic stem cells requires tight DNA compression

It is known that histone H1 mainly functions as a structural component of chromosomes, but this study reveals a new regulatory function of histone H1. This study found that H1 plays a role in controlling the genes that guide the differentiation of embryonic stem cells. In order to expand people's understanding of the function of H1 and provide valuable new insights into the cellular process of inducing stem cells to produce specific types of cells. During automatic differentiation, most of the three H1 subtypes that were studied by researchers were knocked out of embryos Stem cells maintain a tightly packed cell population structure (which is also a typical feature of undifferentiated cells), and express high levels of Oct4 for a long period of time. Oct4 is a pluripotency gene that maintains the self-renewal capacity of embryonic stem cells, so Must be suppressed in order to induce differentiation. Fan explained, "H1 deletion leads to impaired suppression of Oct4 and Nanog pluripotency genes, suggesting that a new link between H1 and chromatin concentration may be through the promotion of pluripotency genes. Epigenetic silencing regulates the differentiation of pluripotent stem cells. Although a significant decrease in H1 levels does not interfere with the self-renewal of embryonic stem cells, it seems to damage Differentiation. "

The researchers also used a rotary suspension culture method developed by Todd McDevitt, an associate professor in the Department of Biomedical Engineering at Georgia Institute of Technology, to efficiently produce homogeneous three-dimensional embryonic stem cell masses called embryo bodies. It usually contains cell types that produce all three germ layers--ectoderm, mesoderm, and endoderm--of which these three germ layers produce multiple tissues and organs in the body. However, most of them are formed by rotating suspension culture The embryonic bodies from which the three H1 subtypes were knocked out cannot produce differentiated structures, and exhibit gene expression patterns typical of undifferentiated stem cells.

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