Human embryonic stem cells (hESCs) are experts are keeping their options open, and now a scientist reports how—it turns out that Oct-4 keeps chromatin in the right state to maintain pluripotency.
In a single-author paper, Xuejun Parsons, who is at the San Diego Regenerative Medicine Institute and Xcelthera, lays it all out. She’d developed a defined culture system for keeping hESCs pluripotent, and she used it to figure out what makes the cells stay that way.
Here’s some of what she found out:
- Undifferentiated hESCs express Oct-4 and have acetylated H3 and H4, as well as lots of active chromatin remodeling factors, like Brg-1, hSNF2H, HAT p300, and HDAC1 in the nucleus.
- Repressive factors were in the cytoplasm or were weakly expressed in undifferentiated cells.
- Cells in the center of a colony were undifferentiated, but were more differentiated toward the edges. Differentiating cells in the zone just outside of the center had lower Oct-4 levels, but high H3 and H4 acetylation. In the outermost areas, the most differentiated cells were actually hypoacetylated on H3 and H4.
- Lowering Oct-4 with siRNA reduced HDAC1 levels. H3 and H4 also were highly acetylated. These cells started differentiating.
In the paper, Parsons explains that this points to a model in which Oct-4 is a global chromatin-remodeling factor that balances acetylating and deacetylating factors so that hESCs have open, acetylated chromatin. Once Oct-4 or HDAC1 decreases, then hyperacetylation happens and differentiation starts.
“This study showed that human embryonic stem cells (hESCs) that display normal stable expansion are not only pluripotent, but also incredibly positive, as evident by that only the positive active chromatin remodeling factors, but not the negative repressive chromatin remodeling factors, can be found in the open epigenome of hESCs. The normality and positivity of hESC open epigenomic landscape also differentiate pluripotent hESCs from any other stem cells, such as the induced pluripotent stem (iPS) cells reprogrammed from adult cells and the tissue-resident stem cells,” added Parsons.
Find out more at Anatomy & Physiology, April 2012.