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Scientists map epigenetic changes during blood cell differentiation
Date:8/16/2010

ssor of Molecular Medicine and director of the Center for Epigenetics at Hopkins' Institute for Basic Biomedical Sciences.

"Genes themselves aren't going to tell us what's really responsible for the great diversity in cell types in a complex organism like ourselves," Feinberg says. "But I think epigeneticsand how it controls genes-can. That's why we wanted to know what was happening generally to the levels of DNA methylation as cells differentiate."

One of the surprising finds was how widely DNA methylation patterns vary in cells as they differentiate. "It wasn't a boring linear process," Feinberg says. "Instead, we saw these waves of change during the development of these cell types."

The data shows that when all is said and done, the lymphocytes had many more methylated genes than myeloid cells. However, on the way to becoming highly methylated, lymphocytes experience a huge wave of loss of DNA methylation early in development and then a regain of methylation. The myeloid cells, on the other hand, undergo a wave of increased methylation early in development and then erase that methylation later in development.

Rudimentary as it is, this first epigenetic landscape map has predictive power in the reverse direction, according to Feinberg. The team could tell which types of stem cells the blood cells had come from, because epigenetically those blood cells had not fully let go of their past; they had residual marks that were characteristic of their lineage.

This project involved a repertoire of talents.."None of whom were more integral than Irv Weissman at Stanford," Feinberg says. "He's a great stem cell biologist and he lent a whole level of expertise that we didn't have."

One apparent application of this work might be to employ these same techniques to assess how completely an induced pluripotent stem cell (iPSC) has been reprogrammed.

"You might want to have an incompletely reprogrammed cell type fro
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Contact: Maryalice Yakutchik
myakutc1@jhmi.edu
443-287-2251
Johns Hopkins Medical Institutions
Source:Eurekalert

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