We are interested in understanding how cell identity is established, maintained, and altered during mammalian (both mouse and human) development. Specifically, our lab studies the molecular control of stem cell potency underlying embryonic stem cell (ESC) pluripotency, somatic cell reprogramming, and totipotency-to-pluripotency transition during early development. We employ both genomic and proteomic approaches as well as mouse models to identify and study protein-protein interaction and transcriptional regulatory networks that govern ESC pluripotency, somatic cell reprogramming, and embryogenesis. Insights from our studies will facilitate efficient generation and optimal propagation of stem cells for their applications in disease therapeutics and regenerative medicine. As misregulation of cell fate causes many diseases including cancer, our studies will also offer mechanistic insights into disease etiology and tumorigenesis.
Pluripotency spans a spectrum of potency states in development encompassing naive, formative and primed pluripotent states (see Figure above), which are typified by in vitro cultures of ESCs, epiblast-like cells (EpiLCs), and epiblast stem cells (EpiSCs), respectively. Pluripotent stem cells serve as a potentially inexhaustible source for tissue replacement in regenerative medicine due to their capability of unlimited self-renewal and multi-lineage differentiation. In contrast to the extensive studies of pluripotency, studies of totipotency are lagging behind due to the difficulty in capturing totipotent stem cells for stable in vitro culture and maintenance. A group of stem cells with totipotency features, collectively known as 2C-like cells (2CLCs) (Macfarlan et al. Nature 487:57-63 (2012)) and expanded potential or extended pluripotent stem cells (EPSCs) (J Yang et al. Nature 550:393-397 (2017); J Yang et al. Nature 550:393-397 (2017)), were captured in culture (see Figure above). At the present, how these cells maintain or acquire totipotency and the exact nature of the cell potency that exists in the zygote and 2-cell stage embryos are still poorly understood.
Our lab is particularly interested in the following five areas of research:
Our lab is particularly interested in the following five areas of research:
