Yu Cai obtained his B.Sc (1993) from Xiamen University, China and Ph.D (2003) from Institute of Molecular and Cell Biology (IMCB) (in Bill Chia/Xiaohang Yang lab), National University of Singapore, Singapore. He spent one year in the same lab as a postdoc before joining Temasek Life Sciences Laboratory (TLL) as a Young Investigator (YI) in 2004. Currently, he is an adjunct assistant professor of Department of Biological Sciences, NUS, Singapore.
You may wish to contact Dr Yu CAI at:Tel: (65) 6872 7000 ,6874 6279 (DID) or 6872 7419 (lab) Email: firstname.lastname@example.org
For information on PhD studies at TLL, click HERE
Stem cells, which can self-renew and give rise to differentiated daughters, are responsible for the generation of diverse cell types during development and the maintenance of tissue/organ homeostasis in adulthood. My laboratory deploys two well-established systems, female germline stem cells and neural stem cells of the model organism Drosophila melanogaster to study stem cell biology in an entire organism (in vivo). The immediate aim is to investigate the underlying mechanisms controlling stem cell self-renewal vs. differentiation during development. The long-term goal is to extrapolate our knowledge to stem cell-based therapy in regenerative medicine and cancer biology.
I. Stem Cell Niche Establishment: In vivo, stem cell self-renewal vs. differentiation is greatly influenced by extrinsic signalings derived from the surrounding tissue-specific microenvironment, the so-called “niche”. Niche promotes stem cell fate by concentrating localized factors including signaling molecules which favor stem cell self-renew and regulate stem cell proliferation in line with developmental programs. We focus on the establishment/maintenance of the germline stem cell niche during fly development. To this end, we have identified several factors including transcription factors, histone modifiers and chromatin remodelers, required for the niche formation/function. We are currently investigating the underlying mechanisms of these factors’ functions.
II. Niche Activity Control: In addition to its role in maintain stem cells, the niche also safeguards against excess stem cell production that could lead to tumor initiation. How is the niche activity spatially restricted? We recently showed that the female germline stem cells and their progeny play an active role in the spatial restriction of the niche activity by preventing active transport of Dpp, a fly TGF-b molecule and the primary niche-associated signaling molecule, outside the niche and identified EGF Receptor signaling as a key signaling involved in this process. We are now addressing how EGFR signaling coordinates with other factors to define the functional range of the niche. These data expand the classic view of the relation between stem cells and their niche with stem cells being a passive signaling receiving entity within the niche and suggest that stem cell lineage is an indispensable component of the niche. Similar interactions between stem cell lineage and their niche are also observed in a wide range of vertebrate stem cell systems.
III. Stem Cell Intrinsic Factors: Niche-associated signals must coordinate with stem cell intrinsic programs to support a stem cell fate. We are also interested in the stem cell intrinsic factors required for stem cell maintenance and have identified several such factors through a large-scale genetic screen.
IV. Stem Cell Regulation during Development: How is stem cell proliferative activity regulated during development? To understand this, we investigate neural stem cells of the developing central nervous system. During Drosophila neurogenesis, the timing generation of specific neurons is controlled by two mechanisms – the temporal series (the sequential switching of transcription factors) and asymmetric cell division. These two mechanisms also coordinate to schedule the end of neurogenesis when the complete nervous system is generated. We recently identified Hh signaling, a conserved developmentally-regulated signal, as a bridge to coordinate these two mechanisms to schedule the timing termination of neurogenesis. Manipulation of Hh signaling activity during Drosophila development could reschedule the timing termination of neurogenesis accordingly. Interestingly, both the temporal series and asymmetric cell division mechanisms have also being identified in the neural stem cells in developing nervous system of vertebrate. Intriguingly, during vertebrate neurogenesis, SHH signaling plays a role to promote exit of neurogenesis. These data suggest a conserved mechanism to control neurogenesis during development across species.