Life Sciences Institute
University of Michigan Medical School
210 Washtenaw Avenue Room 5403
Ann Arbor, MI 48109-2216
2008 Searle Scholar
Molecular and Cellular Mechanisms Governing Stem Cell Behavior
Adult stem cells continuously supply highly differentiated but short-lived cells, such as blood, skin, intestinal epithelium, and sperm cells, throughout life. The daughters of stem cell division have two possible fates: stem cell self-renewal or commitment to differentiation. It is critical to maintain a balance between these cell populations as an excess of stem cell self-renewal can lead to tumorigenesis, whereas an excess of differentiation can deplete the stem cell pool, reducing tissue regenerative capacity. To maintain the balance between stem cells and differentiating cells, many stem cells have the potential to divide asymmetrically so that each division produces one stem cell and one differentiating cell. Although the control of stem cell division is crucial for tissue homeostasis, the mechanisms that regulate asymmetric stem cell division are poorly understood. Furthermore, it has been hypothesized that declining stem cell function contributes to tissue degeneration during aging, although the mechanism by which this occurs and whether it involves changes in stem cell division is unknown.
Our laboratory is investigating the molecular and cellular mechanisms that govern stem cell behavior, in particular, the regulation of asymmetric stem cell division, using Drosophila male germline stem cells (GSCs) as a model system.
Drosophila male germ line stem cells serve as an ideal model system to study stem cell behavior. They reside in the stem cell niche, which specify stem cell identity by sending signal(s). Stem cells have elaborate cellular mechanisms to ensure the asymmetric outcome of the division, producing one stem cell and one differentiating cell, which is the key to tissue homeostasis. We have discovered the cellular mechanisms by which stem cell divide asymmetrically. In one such mechanism, the mother centrosome is maintained close to the Niche-Stem cell interface, while daughter centrosome migrates away from the niche. Such stereotyped behavior of centrosomes prepares the orientation of mitotic spindle in germ line stem cells, so that stem cells always divide perpendicularly to the niche, placing one daughter within and the other outside the niche.
We are also interested in how the centrosome behavior is regulated during the process of aging, leading to a decline in spermatogenesis.2011 MacArthur Fellow
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