Yukiko Yamashita

Question

When a stem cell divides, what determines which daughter cell will remain a stem cell and which will differentiate into another tissue type? What is the function of pericentromeric satellite DNA, which has been regarded as genomic junk?

Approach

The human body depends on stem cells to replenish stocks of highly differentiated but short-lived cells. These include blood, skin, sperm and intestinal epithelial cells. In order to retain the necessary amount of stem cells, the cells themselves have to strike a balance: often, when they divide, one cell remains a stem cell while the other differentiates into something else. If too many stem cells are created, tumors may form, while not enough stem cells can reduce the capacity of tissues to regenerate. Yukiko Yamashita’s lab seeks to understand how cells maintain this balance through four avenues of research. 

One such avenue is the mechanism of asymmetric germline stem cell (or GSC) divisions. These cells -- which Yamashita obtains from male Drosophila fruit flies -- are an ideal model system to study stem cell behavior. GSCs are attached to somatic hub cells, which determine stem cell identity. 

Another area of focus is the stem cell-specific regulation of centrosomes. Many stem cells, including Drosophila male GSCs, utilize unique regulation of centrosomes to divide asymmetrically. Yamashita’s lab is interested in identifying and characterizing stem cell-specific centrosomal components, and their potential roles in asymmetric stem cell division.

The lab also recently discovered that sister chromatids of X and Y chromosomes are distinguished and separated non-randomly during GSC divisions. They are currently interested in understanding the molecular and cellular mechanisms of non-random sister chromatid segregation, and its biological significance.

Finally, Yamashita studies how two stem cell populations coordinate to maintain tissue homeostasis. Many tissues contain multiple stem cell lineages, so in order to maintain a proper balance of cells in the tissue, these populations must coordinate. How exactly they do this, though, is poorly understood. Yamashita is interested in the mechanisms that allow different stem cell populations to communicate. 

An emerging area of interest for the lab is the function of satellite DNA. Despite its ubiquity and abundance, it has been regarded as genomic junk. The lab’s recent discovery led to a proposal that satellite DNA plays a critical role in packaging the full complement of chromosomes into a single nucleus, a universal feature of eukaryotic cells. 

Bio

Yamashita earned both her B.S. in Biology (1994) and her Ph.D. in Biophysics (1999) from Kyoto University, where she conducted her graduate research in the lab of Mitsuhiro Yanagida. From 2001 to 2006, she did postdoctoral research in developmental biology in Margaret Fuller’s lab at Stanford University. She was appointed to the Michigan faculty in 2007 and was named an HHMI Investigator in 2014. She became a Member of Whitehead Institute and a professor of biology at MIT in 2020.