Disease Programs

Germline Stem Cells

Robert Braun (Genome Sciences)

Several published studies suggest that adult germline stem cells and embryonic stem cells are developmentally related and have overlapping properties. Both cell types are derived from early embryos and one hypothesis specifically states that embryonic stem cells are derived from primordial germ cells— the precursors of adult germline stem cells. In cell culture and transplantation studies it has been shown that embryonic stem cells can give rise to germ cells. Perhaps more remarkably, it has recently been reported that postnatal germline stem cells can "revert" to a pluripotent germline stem cell that has many of the properties of embryonic stem cells. This finding suggests that adult germline stem cells may be an alternative to embryonic stem cells for transplantation therapy and regenerative medicine. Dr. Braun's lab is actively investigating the mechanism of adult germline stem cell self-renewal in the mouse. Using a genetic approach, the lab has shown that the Promyelocytic leukemina zinc finger (Plzf) protein is required for adult germline stem cell self-renewal. Loss of Plzf function shifts the balance between stem cell self-renewal and differentiation—toward differentiation at the cost of self-renewal. Several studies have shown that Plzf directly regulates the epigenetic repression of chromatin domains required for cell differentiation. Recent work in the Braun lab has shown that germline stem cells have a unique pattern of methylated histones and that this pattern is altered in cells lacking Plzf. Current studies are aimed at investigating how germline stem cells integrate extracellular signals from their somatic niche to regulate the expression of Plzf and other proteins required for germline stem cell self-renewal. Long-term studies are directed at investigating the pluripotency phenotype shared by germline and embryonic stem cells.

Hannele Ruohola-Baker (Biochemistry)

This group has recently shown that Dcr-1-deficient germ line stem cells are delayed in the CDK-inhibitor We p21/p27/Dacapo-dependent G1/S transition, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint (Hatfield et al., 2005, Nature). Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition. Since miRNAs are a novel class of genes involved in human tumorgenesis , it is tempting to speculate that miRNAs could play a similar role in cancer cells. The investigator is now moving towards analyzing micro RNA function in human

Billie Swalla (Biology)

I am working on stem cells in colonial ascidians, which circulate in the blood and are necessary both to form a new individual asexually, and for gametes to develop in the ovary and testes. We are developing molecular markers to identify various stem cells circulating in the blood, in order to understand their potential.

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