Skin epithelial stem cell fate maintenance and lineage determination
Our lab's main interest is to understand the molecular mechanisms of self-renewal and differentiation of stem cells. We use the mammalian skin as a model system to study stem
cells, because skin is a self-renewing tissue whose large pool of stem cells are regularly activated throughout the animal's lifespan. Wnt signaling pathway plays an important role in many
developmental processes, including self-renewing and differentiation of stem cells. Depending on the cofactors that are present, the transcription factors Tcf3 and Tcf4 can either repress or
activate Wnt-responsive genes. Previously, we found that both Tcf3 and Tcf4 are expressed in embryonic and adult epidermal stem cells, and that they play a crucial role in maintaining the
self-renewal capacity of stem cells.
We are currently pursuing the following questions: 1) What are the target genes of Tcf3/4 that are responsible for maintaining the undifferentiated state of stem cells and how do these
genes exert that function? 2) What are the regulatory factors that turn on Tcf3/4 expression in skin stem cells, and conversely what repressive factors turn them off in committed cells? 3)
How are these genes altered during the aging process and how they are dysregulated in different diseases?
Answering these questions will provide a deeper understanding of how stem cells maintain their multipotent status and control cell fate specification. Since cancer cells often display
many characteristics of stem cells, studying the molecular mechanisms of how stem cells maintain their multipotent undifferentiated state is important for regenerative medicine as well as
for the development of anti-cancer therapeutics.
Selected Publications
Nguyen H, Merrill BJ, Polak L, Nikolova M, Rendl M, Shaver TM, Pasolli HA, Fuchs E (2009) Tcf3 and Tcf4 are essential for long-term homeostasis of skin epithelia.
Nature Genetics 41: 1068-1075.
Nguyen H, Rendl M, Fuchs E (2006) Tcf3 governs stem cell features and represses cell fate determination in skin. Cell 127:171-183.
Liu Y, Hedvat CV, Mao S, Zhu XH, Yao J, Nguyen H, Koff A, Nimer SD (2006) The ETS protein MEF is regulated by phosphorylation-dependent proteolysis via the
protein-ubiquitin ligase SCFSkp2. Molecular and Cellular Biology 26:3114-3123.
Zhu XH, Nguyen H, Halicka HD, Traganos F, Koff A (2004) Noncatalytic requirement for cyclin A-cdk2 in p27 turnover. Molecular and Cellular Biology
24:6058-6066.
Nguyen H, Gitig DM, Koff A (1999) Cell-free degradation of p27kip1, a G1 cyclin-dependent kinase inhibitor, is dependent on CDK2 activity and the proteasome.
Molecular and Cellular Biology 19:1190-1201.
Millard SS, Yan JS, Nguyen H, Pagano M, Kiyokawa H, Koff A (1997) Enhanced ribosomal association of p27Kip1 mRNA is a mechanism contributing to accumulation during
growth arrest. Journal of Biological Chemistry 272:7093-7098.
Contact Information
- Hoang Nguyen, Ph.D.
- Department of Molecular and Cellular Biology
- Center for Cell and Gene Therapy
- Baylor College of Medicine
- One Baylor Plaza N1120
- Houston, Texas 77030, U.S.A.
- Tel: (713) 798-1236
- Fax: (713) 798-1230
- E-mail: hoangn@bcm.edu
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