New Faculty

Two recent papers by CIRM grantees highlight the importance of understanding basic stem cell biology while developing new cures. Both have to do with chemical modifications to the DNA – called epigenetics.

One of the two papers shows that an epigenetic change in DNA, called methylation, changes dramatically as human embryonic stem cells mature into specific cell types; the other shows that even subtle DNA methylation differences alter the way a cell behaves.

Researchers at the Stanford University School of Medicine have found that a gene long-known to regulate the lifespan of tiny roundworms also plays a role in regulating neural stem cells in mice.

Variations of the gene family, called FoxO, help roundworms live to an unusually ripe old age in the lab, and mutations in the FoxO3 gene have also recently been associated with long life in Japanese, German, American and Italian populations. Laboratory mice lacking FoxO3 live to about half their usual age of 30 months before dying of cancer.

Researchers at the University of California, Berkeley have found molecular pathways that human muscle stem cells rely on to repair damaged muscle. These pathways are active in younger people but less active in older people, explaining why muscles repair more slowly with age. The group found that younger volunteers had double the number of regenerative muscle stem cells in their thigh muscles compared to older volunteers. After two weeks in a leg cast, both groups began exercise routines to rebuild muscle.

Researchers at the University of California, San Francisco have pinpointed a protein that is critical for maintaining a stem cell's full potential to self-renew and to differentiate. Stem cells lacking the protein were impaired in their ability to divide and make identical copies of themselves, called self-renewal. These cells also lost their capacity to differentiate into key cell types, such as cardiac muscle. The protein, Chd1, acts to keep chromosome strands loosely wound, which permits widespread gene activation in the cell's nucleus.

Researchers at the University of California, Los Angeles have found genetic differences that distinguish induced pluripotent stem (iPS) cells from embryonic stem cells. These differences diminish over time, but never disappear entirely. iPS cells are created when adult cells, such as those from the skin, are reprogrammed to look and behave like embryonic stem cells. But until now, scientists didn't know if the two types of stem cells were actually identical at a molecular level. This latest research shows that iPS and embryonic stem cells differ in which genes they have turned on or off.

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