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Research

1. Genetic control of hematopoietic stem cell development.

We are studying molecular mechanisms of HSC emergence and maintenance including the key signal transduction pathways, gene regulatory network (GRN) and epigenetic modification, in order to better understand programming/reprogramming of these cells for potential therapeutic application. Our studies showed that may factors or signaling pathways play important role in HSC development, such as G protein-coupled receptor, inflammatory signaling, ERK signaling, Ncor2, Fev and miR142-3p. Meanwhile, Blood flow is essential for the maintenance of HSC programming through KLF2-NO signaling cascade.

2. Molecular regulation of T cell specification and erythroid maturation.

We are also interested in HSC differentiation. Recently, we found that Irf4 regulates the choice between T lymphoid-primed progenitor and myeloid lineage fates during embryogenesis. We also reported that Foxn1 plays an essential role during thymopoiesis in zebrafish to maintain TEC and T cell development through direct regulation of mcm2. In addition, two Klf family genes are demonstrated to be important for erythroid maturation in zebrafish.

To obtain functional HSCs in vitro is a major goal of basic research in hematopoiesis and holds great promise in regenerative medicine. However, production of transplantable HSCs in vitro has not yet been achieved. The bottleneck for this is that the molecular regulation of HSC development (emergence, maintenance and differentiation) in vivo is still poorly understood. Our ongoing and future work focuses on molecular mechanisms underlying HSC development in vivo and how to make functional HSCs in vitro. The research findings in our lab will expand our understanding on the gene regulatory network of HSC development in vertebrates, and will provide new insights into the in vitro generation of transplantable HSCs for potential clinical applications.

     

 
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