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Pluripotent Stem Cells: molecular mechanism that regulates self-renewal and pluripotency.
Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), can be perpetually propagated in vitro while maintaining the developmental potential to form tissues from all three germ layers. These two defining properties of PSCs, namely self-renewal and pluripotency, provide unique opportunities to model early embryonic development and generate tissues for regenerative medicine. The recent success in iPSCs paved the way to generate human histocompatible PSCs by reprogramming patients’ own somatic cells. When transplanted, tissues derived from the patient-specific PSCs would induce no or little immune rejection. The iPSC-technology also allowed generation of disease-specific PSCs that could serve as a novel platform for human disease modeling and drug screening.
The research of my lab will focus on the biology of pluripotent stem cells (PSCs). We would like to understand how PSCs remain to be PSCs (self-renewal), how terminally differentiated somatic cells become iPSCs (reprogramming) and how disease-specific iPSCs recapitulate human disease progression in tissue culture dishes (disease modeling).
Questions we are addressing include:
(1) In PSCs, how self-renewal is achieved? What are the roles of pluripotency-promoting factors in maintaining the
identity of PSCs? How PSCs exit the pluripotent state when induced for differentiation?
(2) In the transition of terminally differentiated somatic cells to iPSCs, how the defined transcription factors initiate
the cascade of events that lead to pluripotency? Is the reprogramming process stochastic or stepwise?
If stepwise, what are the intermediate stages? How can we improve the reprogramming technology? How
pluripotency is established?
(3) Does differentiation of the iPSCs derived from diseased human somatic cells recapitulate disease progression?
What can we learn about the human disease from this in vitro modeling system? Can we further turn the in vitro
modeling system into a platform to test or screen drugs for the human disease?
An improved understanding on the basic biology of PSCs will be essential to harness the full potential of PSCs
in applications such as regenerative medicine, human disease modeling and drug screening. Our research will
potentially lead to safer and more efficient uses of PSCs in human disease modeling and treatment.