Hong Kong University of Science and Technology, Hong Kong
Abstract: Stem cells are a group of cells with unique capacities to self-renew and differentiate into specialized cells, which are vital for the maintenance of tissue homeostasis throughout the lifespan under the regulation of their niche. Despite the well-known importance of stem cell-niche interactions in tissue maintenance, the molecular mechanisms underlying their roles in various biological processes and diseases are not yet fully understood. Here, we made use of fruit fly (Drosophila melanogaster), zebrafish (Danio rerio), nematode (Caenorhabditis elegans), mouse (Mus musculus), and human induced pluripotent stem cells (iPSCs) as a model to comprehensively investigate the stem cell-niche interactions in tissues maintenance and ultimately engineer niche and stem cell-based tissues. In the last year of the project, 1) we have identified new secreted niche factors (NetA and NetB) for germline stem cells (GSC) self-renewal, new niche factors for GSC progeny differentiation (condensin II and Mirror), and 29 new niche factors (e.g., Tet, BAP55, BAP111, and Pus1) involved in controlling germline stem cells (GSC) aging using Drosophila ovary. 2) Besides, we also investigated intrinsic factors, ATF3 and H2B in muscle stem cell (MuSC) activation and proliferation and uncovered two intrinsic factors, JUNB and CCR5, for driving MuSC aging using Zmpste24 mutant mice and human samples. 3) On the other hand, biotechnologies, including somatic niche cell co-culturing, B12-dependent photo-regulatable proteins, and SpyTagged spider silk protein have been developed in our project to build up the artificial niche for stem cell maintenance and expansion in vitro. Taken together, these findings enable a deeper understanding of stem cell-niche interactions in biological processes and diseases, providing solid evidence for further development of therapeutic strategies targeting stem cells and their niche.
Funding Source: RGC Theme-based Research Scheme (T13-602/21N)
