Yamashita Lab Research

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 self-renewal and differentiation, as an excess of stem cell self-renewal can lead to tumorgenesis, 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. Furthermore, all multi-cellular organisms, including ourselves, have developed from a single cell (i.e. zygote) by a series of asymmetric cell divisions that create daughter cells with distinct cell fates. In spite of its fundamental importance, the mechanisms by which cells undergo asymmetric divisions are poorly understood.

Our laboratory is interested in understanding the mechanisms of asymmetric cell division, in particular that of stem cells, using Drosophila male germline stem cells (GSCs) as a model system. Drosophila male GSCs serve as an ideal model system to study stem cell behavior. GSCs are attached to somatic hub cells, which functions as the major component of the stem cell niche that specifies stem cell identity.

Our current research focuses on the following subjects:

1)    The mechanism of asymmetric GSC divisions: we have shown that GSCs divide asymmetrically by orienting their mitotic spindle perpendicular to the hub cells. The difference(s) between mother and daughter centrosomes underlie the asymmetric behavior of two centrosomes in preparation of spindle orientation. We are interested in how GSCs ensure oriented cell division, including a novel checkpoint that monitors correct centrosome orientation.

2)    The stem cell-specific regulation of centrosome: it has been shown that many stem cells, including Drosophila male GSCs, utilize unique regulation of centrosomes to divide asymmetrically. We are interested in identifying and characterizing stem cell-specific centrosomal components, and their potential roles in asymmetric stem cell division.

3)    Non-random sister chromatid segregation during GSC division: we have recently shown that sister chromatids of X and Y chromosomes are distinguished and segregated non-randomly during GSC divisions. We are interested in understanding the molecular and cellular mechanisms of non-random sister chromatid segregation, and its biological significance.

4)  Coordination between two stem cell populations to maintain tissue homeostasis: many tissues contain multiple stem cell lineages, and therefore the coordination of proliferation among distinct stem cell populations is essential for maintaining tissue homeostasis. Yet, the underlying mechanisms are poorly explored. We are interested in deciphering the mechanisms that allow stem cell populations to communicate each other to coordinate their proliferations.

            

Yamashita Lab Members