CDE: [The Dean’s Speaker Series] Skeletal Stem Cells: From Development & Disease to Regenerative Medicine

Virtually via Bluejeans

Time: 12:00 – 1:00 pm
Registration Fee: Free; Registration is required for CE credit.
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CE Credits: 1.0 lecture credits

Description

The craniofacial skeleton consists of viscerocranium and neurocranium, which is subdivided into the calvarium and chondrocranium. During calvarial development, sutures serve as the growth center for skeletogenesis. Defects in suture morphogenesis resulting in premature closure cause a devastating childhood disease – Craniosynostosis.

Although human genetic analyses have identified genes associated with the pathogenesis, the mechanism underlying suture closure remains largely elusive. My lab found that Axin2 deficiency in mice causes craniosynostosis. Axin2 regulates suture morphogenesis and skeletogenesis through modulation of the Wnt pathway. Axin2-mediated Wnt regulation controls signaling crosstalk of BMP and FGF required for skeletal cell fate determination. Proteomic approaches discover the small GTPase Rap1b as a downstream effector of Axin2 that balances the interplay of BMP and FGF signaling.

The stem cell population residing in the suture mesenchyme has been successfully identified and isolated in my lab. These suture stem cells (SuSCs) are responsible for calvarial development in infants as well as homeostatic maintenance in adults. Upon injury, the dormant SuSCs respond quickly and contribute directly to bone repair in a cell autonomous fashion. An in vivo clonal analysis of SuSCs further demonstrates bone regeneration at a single-cell level.

Implantation of SuSCs to an injured site shows not only long-term survival but also facilitation of bone healing via direct engraftments in which the implanted stem cells give rise to osteogenic cell types in replacement of the damaged tissue. The scRNA-Seq further dissects the SuSC population and identifies the cell surface marker potentially used for its isolation from human skulls.

We are able to move a step closer to clinical applications by studying human SuSCs and maintaining their stemness in vitro. The newly discovered SuSC thus has outstanding potential to gain novel insights into the etiology of craniosynostosis. They also promise cell-based skeletal regeneration, leading to repairment of large bone defects caused by various conditions over 2.2 million cases worldwide each year.

Objectives

• Calvarium as a model for the study of development and disease, stem cell biology and regenerative medicine
• Mouse genetic models for the study of development and disease
• The interplay of signaling pathways in skeletal cell fate determination
• Identification of a novel stem cell population in calvarial development, homeostasis, and injury-repair
• Isolation of skeletal stem cells in mice and human for bone regeneration and repair

Speaker

Wei Hsu, PhD.,
Dean’s Professor of Biomedical Genetics
Center for Oral Biology
University of Rochester Medical Center

Dr. Wei Hsu received his Ph.D. at Mount Sinai Medical Center in New York City. He did a postdoctoral fellowship at Columbia University College of Physicians and Surgeons, subsequently promoted to research faculty. Dr. Hsu moved to the University of Rochester Medical Center where he has been a faculty member since 2002.

He is currently Dean’s Professor of Biomedical Genetics in the Center for Oral Biology. Dr. Hsu’s lab is interested in the elucidation of mechanisms underlying embryonic morphogenesis, tissue homeostasis and disease pathogenesis. His recent study mainly focuses on craniofacial and skeletal development as well as congenital birth defects and the study of skeletal stem cells and stem cell-mediated regeneration and repair.

Dr. Hsu is a renowned researcher in the field of Wnt signaling. He is well-known for the identification of Axin, the repressor of beta-catenin in Wnt signal transduction as well as the finding of Gpr177, the mouse orthologue of Drosophila Wntless essential for the secretion Wnt proteins. His research program is continuously funded by NIH for two decades.

Dr. Hsu is also a co-director of an NIH funded Training Program for Oral Health Science and has trained more than 30 students and postdocs with many of them holding principal investigator positions in academic and research-oriented institutions. He has provided an enormous amount of services for national and international committees (NIH, DOD, Medical Research Council of UK, Japanese Society for Promotion of Science, A*STAR of Singapore, Dutch Cancer Society, Telethon Foundation of Italy), editorial board (Journal of Dental Research), and review panels for high impact journals. Dr. Hsu has given more than 70 invited lectures at research conferences and leading biomedical institutions.

Disclosure: Dr. Wei Hsu has no relevant financial interests.

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University of Pennsylvania School of Dental Medicine designates this activity for 1.0 continuing education credits.