Cell and Developmental Biology University of Michigan

Research

Interested in understanding how stem cells utilize cell biological mechanisms, which are shared with most cell types, yet in a stem cell-specific way, to accomplish stem cells' function. We study how stem cells orient their division plane in the context of signaling microenvironment to divide asymmetrically, how such process is monitored, and how it changes during aging.

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 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. 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; one such mechanism is depicted above: The mother centrosome (red and green) is maintained close to the Niche (blue line)-Stem cell (dotted line) interface, while daughter centrosome (red but not green) 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.

Lab Members

• Mayu Inaba
  Research Fellow
• Therese Roth
  Research Fellow
• Hebao Yuan
  Research Fellow
• Chieh-Yin Chiang
  Research Associate
• Victoria Salzmann
  Research Associate
• Swathi Yadlapalli
  Graduate Student
• Heiko Yang
  Graduate Student

Publications

Representative Publications

1. Pereira G, Yamashita YM. Fly meets yeast: checking the correct orientation of cell division. Trends Cell Biol. 2011 Sep;21(9):526-33. Epub 2011 Jun 24. PubMed PMID: 21705221.
2. Yadlapalli S, Cheng J, Yamashita YM. Drosophila male germline stem cells do not asymmetrically segregate chromosome strands. J Cell Sci. 2011 Mar 15;124(Pt 6):933-9. Epub 2011 Feb 15. PubMed PMID: 21325028; PubMed Central PMCID: PMC3048890.
3. Cheng J, Tiyaboonchai A, Yamashita YM, Hunt AJ. Asymmetric division of cyst stem cells in Drosophila testis is ensured by anaphase spindle repositioning. Development. 2011 Mar;138(5):831-7. PubMed PMID: 21303845; PubMed Central PMCID: PMC3035088.
4. Yuan H, Yamashita YM. Germline stem cells: stems of the next generation. Curr Opin Cell Biol. 2010 Dec;22(6):730-6. Review. PubMed PMID: 20817500; PubMed Central PMCID: PMC2993778.
5. Inaba M, Yuan H, Salzmann V, Fuller MT, Yamashita YM. E-cadherin is required for centrosome and spindle orientation in Drosophila male germline stem cells. PLoS One. 2010 Aug 31;5(8):e12473. PubMed PMID: 20824213; PubMed Central PMCID: PMC2930853.
Yamashita YM. Cell adhesion in regulation of asymmetric stem cell division. Curr Opin Cell Biol. 2010 Oct;22(5):605-10. Epub 2010 Aug 17. Review. PubMedPMID: 20724132; PubMed Central PMCID: PMC2948594.