"H1 triple-knockout embryoid bodies displayed a reduced level of activation of many developmental genes and markers in rotary culture, suggesting that differentiation to all three germ layers was affected." noted McDevitt.
The embryoid bodies also lacked the epigentic changes at the pluripotency genes necessary for differentiation, according to Fan.
"When we added one of the deleted H1 subtypes to the embryoid bodies, Oct4 was suppressed normally and embryoid body differentiation continued," explained Fan. "The epigenetic regulation of Oct4 expression by H1 was also evident in mouse embryos."
In another experiment, the researchers provided an environment that would encourage embryonic stem cells to differentiate into neural cells. However, the H1 triple-knockout cells were defective in forming neuronal and glial cells and a neural network, which is essential for nervous system development. Only 10 percent of the H1 triple-knockout embryoid bodies formed neurites and they produced on average eight neurites each. In contrast, half of the normal embryoid bodies produced, on average, 18 neurites.
In future work, the researchers plan to investigate whether controlling H1 histone levels can be used to influence the reprogramming of adult cells to obtain induced pluripotent stem cells, which are capable of differentiating into tissues in a way similar to embry
|Contact: Abby Robinson|
Georgia Institute of Technology Research News