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Biochemistry Experts

Li Jinsong

Professor
Biochemistry and Cell Biology
Shanghai Institutes for Biological Sciences
China

Biography

LI Jinsong is a Professor of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, hanghai, China. Research Areas: Cellular reprogramming; cloning; nuclear transfer; induced pluripotent stem cell (iPS cell); haploid ESCs; semi-cloned technology; embryonic development. Research Interests: Somatic reprogramming induced by iPSC and nuclear transfer (NT) technologies has offered exciting promises in basic and applied research. However, there are three major problems in this field, i.e., 1) the efficiency is very low; 2) the quality of iPSCs is low; and 3) the underlying mechanisms are not clear. My lab attempts to optimize reprogramming procedures, improve the developmental potential of reprogrammed cells and reveal the molecular mechanisms involved in somatic reprogramming. In 2012, we reported that the generation of androgenetic haploid embryonic stem cells (AG-haESCs) that can support full-term embryonic development upon injection into MII oocytes, leading to the generation of semi-cloned (SC) mice. However, one major drawback of this study is the frequently observed aberrant development of AG-haESC-derived embryos and the very low birth rate of healthy SC mice (around 2% of total SC embryos); this greatly restricts the applications of AG-haESCs. Recently, we have shown that AG-haESCs carrying deletions in the DMRs (differentially DNA methylated regions) controlling two paternally repressed imprinted genes, H19 and Gtl2, designated as DKO-AG-haESCs, can efficiently support the generation of SC pups at a rate of 20%. We propose that this new technology is feasible for medium-scale targeted screening at organism level, especially for developmental phenotypes, using the appropriate sgRNA libraries targeting preselected candidate genes. We will test this hypothesis and will study the development of primordial germ cells (PGCs) in vivo using “spermatid-like” haploid cell-mediated genetic screening system.

Research Interest

Somatic reprogramming induced by iPSC and nuclear transfer (NT) technologies has offered exciting promises in basic and applied research. However, there are three major problems in this field, i.e., 1) the efficiency is very low; 2) the quality of iPSCs is low; and 3) the underlying mechanisms are not clear. My lab attempts to optimize reprogramming procedures, improve the developmental potential of reprogrammed cells and reveal the molecular mechanisms involved in somatic reprogramming. In 2012, we reported that the generation of androgenetic haploid embryonic stem cells (AG-haESCs) that can support full-term embryonic development upon injection into MII oocytes, leading to the generation of semi-cloned (SC) mice. However, one major drawback of this study is the frequently observed aberrant development of AG-haESC-derived embryos and the very low birth rate of healthy SC mice (around 2% of total SC embryos); this greatly restricts the applications of AG-haESCs. Recently, we have shown that AG-haESCs carrying deletions in the DMRs (differentially DNA methylated regions) controlling two paternally repressed imprinted genes, H19 and Gtl2, designated as DKO-AG-haESCs, can efficiently support the generation of SC pups at a rate of 20%. We propose that this new technology is feasible for medium-scale targeted screening at organism level, especially for developmental phenotypes, using the appropriate sgRNA libraries targeting preselected candidate genes. We will test this hypothesis and will study the development of primordial germ cells (PGCs) in vivo using “spermatid-like” haploid cell-mediated genetic screening system.

Publications

  • Zhong C#, Yin Q#, Xie Z#, Bai M#, Dong R#, Tang W, Xing Y, Zhang H, Yang S, Chen L-L, Bartolomei MS, Ferguson-Smith A, Li D, Yang L*, Wu Y*&Li Jinsong*. CRISPR-Cas9-mediated genetic screening in mice with haploid embryonic stem cells carrying a guide RNA library. Cell Stem Cell2015, 17, 221-232.

  • Bosley KS, Botchan M, Bredenoord AL, Carroll D, Charo RA, Charpentier E, Cohen R, Corn J, Doudna J, Feng G, Greely HT, Isasi R, Ji W, Kim J, Knoppers B, Lanphier E, Li Jinsong, Lovell-Badge R, Martin GS, Moreno J, Naldini L, Pera M, Perry A, Venter JC, Zhang F & Zhou Q. CRISPR germline engineering-the community speaks. Nature Biotechnology 2015, 33, 5, 478-486.

  • Wu K,Zhong C,Chen T,Zhang X,Tao W,Zhang J,Li H,Zhao H.Li J,Chen ZJ.Polar bodies are efficient donors for reconstruction of human embryos for potential mitochondrial replacement therapy.Cell Res. 2017 Aug;27(8):1069-1072.

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