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Faculty

Research Areas
State Key Laboratory of Molecular Biology
State Key Laboratory of Cell Biology
Principal Investigators
Center for Cell Signaling
National Center for Protein Science Shanghai
Members of CAS, CAE
National Outstanding Young Scientists Award
100 Talents Program of the CAS
 
Address: 320 Yue Yang Road, Shanghai 200031, P.R. China
Tel: 86-21-54920000
Fax: 86-21-54921011
Email: sibcb@sibs.ac.cn
Website: www.sibcb.ac.cn
¡¡
Principal Investigators
¡¡
LI Jinsong
Ph.D., Professor
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China.
Tel: 54921422
Email: jsli@@sibcb.ac.cn

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.

Selected Publications

  1. 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.
  2. 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. (Feature)
  3. Liu P, Dou X, Liu C, Wang L, Xing C, Peng G, Chen J, Yu F, Qiao Y, Song L, Wu Y, Yue C, Li Jinsong, Han J, Tang K & Jing N. Histone deacetylation promotes mouse neural induction by restricting Nodal-dependent mesendoderm fate. Nature Communications 2015, 6: 6830.
  4. Qin Y, Qin J, Zhou C, Li Jinsong& Gao W. Generation of embryonic stem cells from mouse adipose-tissue derived cells via somatic cell nuclear transfer. Cell Cycle 2015, 14: 1282-1290.
  5. Zhu W, Yao X, Liang Y, Liang D, Song L, Jing N, Li Jinsong& Wang G*. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling. Development 2015, 142: 465-476. Epub Jan 6. pii: dev.112946.
  6. Wu Y#, Zhou H#, Fan X#, Zhang Y#, Zhang M#, Wang Y, Xie Z, Bai M, Yin Q, Liang D, Tang W, Liao J, Zhou C, Liu W, Zhu P, Guo H, Pan H, Wu C, Shi H, Wu L*, Tang F* &Li Jinsong*. Correction of a genetic disease by CRISPR-Cas9-mediated gene editing in mouse spermatogonial stem cells. Cell Res 2015, 25: 67-79. Epub 2014 Dec 5.
  7. LianX£¬ Xu J£¬Li Jinsong& Chien K. Next-generation models of human cardiogenesis via genome editing. Cold Spring Harb Perspect Med 2014 Sep 18;4(12). pii: a013920. doi: 10.1101/cshperspect.a013920.
  8. Guo F#, Li X#, Liang D#, Li T#, Zhu P, Guo H, Wu X, Wen L, Gu T, Hu B, Walsh CP, Li Jinsong*, Tang F* & Xu G*. Active and passive demethylation of male and female pronuclear DNA in the mammalian zygote. Cell Stem Cell 2014, 15: 447-458.[Epub ahead of print].
  9. Zhang M, Zhou H, Zheng C, Xiao J, Zuo E, Liu W, Xie D, Shi Y, Wu C, Wang H, Li D & Li Jinsong. The roles of testicular c-kit positive cells in de novo morphogenesis of testis. Sci Rep 2014, 4: 5936.
  10. Zhu Q, Song L, Peng G, Sun N, Chen J, Zhang T, Sheng N, Tang W, Qian C, Qiao Y, Tang K, Han JD, Li Jinsong& Jing N. The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways. Elife 2014, Jun 14:e02224. doi: 10.7554/eLife.02224. [Epub ahead of print].
  11. Zhao B, Yang D, Jiang J, Li Jinsong, Fan S, Huang M, Fan Y, Jin Y & Jin Y. Genome-wide mapping of miRNAs expressed in embryonic stem cells and pluripotent stem cells generated by different reprogramming strategies. BMC Genomic 2014, 15: 488.
  12. Yu Y, Liang D, Tian Q, Chen X, Jiang B, Chou BK, Hu P Cheng L, Gao P, Li Jinsong& Wang G. Stimulation of somatic cell reprogramming by Eras-Akt-Foxo1 signaling axis. Stem Cells 2014,32(2): 349-363. doi: 10.1002/stem.1447. [Epub ahead of print].
  13. Qin Y, Zhou P, Zhou C, Li Jinsong& Gao W. The adipose-derived lineage-negative cells are enriched mesenchymal stem cells and promote limb ischemia recovery in mice. Stem Cells Dev 2014, 23: 363-371.
  14. Wu Y#, Liang D#, Wang Y, Bai M, Tang W, Bao S, Yan Z, Li D &Li Jinsong*. Correction of a genetic disease in mouse via use of CRISPR-Cas9. Cell Stem Cell 2013, 13: 659-662.
  15. Yang H#, Liu Z#, Ma Y#, Zhong C, Yin Q, Zhou C, Shi L, Cai Y, Zhao H, Wang H, Tang F, Wang Y, Zhang C, Liu X, Lai D, Jin Y*, Sun Q* &Li Jinsong*. Generation of haploid embryonic stem cells from Macaca fascicularis monkey parthenotes. Cell Res 2013, 23: 1187-1200.
  16. Qin Y#, Lin J#, Zhou C#, Yin Q, Xie Z, Zhang X, Liu X, Gao W &Li Jinsong*. Mice cloned from white adipose tissue-derived cells. J Mol Cell Biol 2013, 5: 348-350.
  17. Jiang J#, Lv W#, Ye X, Wang L, Zhang M, Yang H, Okuka M, Zhou C, Zhang X, Liu L* & Li Jinsong*. Zscan4 promotes genomic stability during reprogramming and dramatically improves the quality of iPS cells as demonstrated by tetraploid complementation. Cell Res2013, 23: 92-106.
  18. Zhao S#, Gou LT#, Zhang M#, Zu LD, Hua MM, Hua Y, Shi HJ, Li Y, Li Jinsong, Li DS, Wang ED* & Liu M. piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis. Dev Cell 2013, 24: 13-25.
  19. Yang H#, Shi L#, Wang B#, Liang D, Zhong C, Liu W, Nie Y, Liu J, Zhao J, Gao X, Li D, Xu G-L*&Li Jinsong*. Generation of genetically modified mice by oocyte injection of androgenetic haploid embryonic stem cells. Cell 2012, 149(3): 605-617.
  20. Shi L, Yang H &Li Jinsong*. Haploid embryonic stem cells: an idea tool for mammalian genetic analyses. Protein & Cell 2012, 3: 806-810. (Invited review)
  21. Ma Y, Gu J, Li C, Wei X, Tang F, Shi G, Jiang J, Kuang Y, Li Jinsong, Wang Z, Xie X & Jin Y. Human foreskin fibroblast produces interleukin-6 to support derivation and self-renewal of mouse embryonic stem cells.Stem Cell Res Ther 2012, 3: 29.
  22. Gu TP#, Guo F#, Yang H#, Wu HP, Xu GF, Liu W, Xie ZG, Shi L, He X, Jin SG, Iqbal K, Shi YG, Deng Z, Szabo PE, Pfeifer GP, Li Jinsong* & Xu GL*. The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 2011, 477, 606-610.
  23. Jiang J#, Ding G#, Lin J#, Zhang M, Shi L, Lv W, Yang H, Xiao H, Pei G, Li Y, Wu J* &Li Jinsong*. Different developmental potential of pluripotent stem cells generated by different reprogramming strategies. J Mol Cell Biol2011, 3: 197-199.
  24. Lin J, Shi L, Zhang M, Yang H, Qin Y, Zhang J, Gong D, Zhang X, Li D &Li Jinsong*. Defects in trophoblast cell lineage account for the impaired in vivo development of cloned embryos generated by somatic nuclear transfer. Cell Stem Cell2011, 8: 371-375.
  25. Yang H#, Shi L#, Chen D &Li Jinsong*. Mice generated after round spermatid injection into haploid two-cell blastomeres. Cell Res2011, 21: 854-858.
  26. Li X, Zhu L, Yang A, Lin J, Tang F, Jin S, Wei Z, Li Jinsong&Jin Y. Calcineurin-NFAT signaling critically regulates early lineage specification in mouse embryonic stem cells and embryos. Cell Stem Cell 2011 8: 46-58.
  27. Wang Y, Chen J, Hu J, Wei X, Qin D, Gao J, Zhang L, Jiang J, Li Jinsong, Liu J, Lai K, Kuang X, Zhang J, Pei D & Xu G. Reprogramming of mouse and human somatic cells by high-performance engineered factors.EMBO Rep 2011, 12: 373-378.
  28. Yang H, Shi L, Zhang S, Ling J, Jiang J&Li Jinsong*. High-efficiency somatic reprogramming induced by intact MII oocytes.Cell Res 2010, 20, 1034-42.
  29. Li L, Sun L, Gao F, Jiang J, Li C, Gu J, Wei Z, Yang A, Lu R, Ma Y, Tang F, Kwon SW, Zhao Y, Li Jinsong& Jin Y. Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation. Proc Natl Acad Sci USA 2010, 107(4):1402-1407.
  30. Chen T, Yuan D, Wei B, Jiang J, Kang J, Ling K, Gu Y, Li Jinsong, Xiao L& Pei G. E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. Stem Cells2010, 28: 1315-1325.
  31. Zhu Z, Wang Y, Li X, Wang Y, Xu L, Wang X, Sun T, Dong X, Chen L, Mao H, Yu Y, Li Jinsong, Chen PA&Chen CD. PHF8 is a histone H3K9me2 demethylase regulating rRNA synthesis.Cell Res2010, 20: 794-801.
  32. Li C, Yu H, Ma Y, Shi G, Jiang J, Gu J, Yang Y, Jin S, Wei Z, Jiang H, Li Jinsong& Jin Y. Germliine-competent mouse-induced pluripotent stem cell lines generated on human fibroblasts without exogenous leukemia inhibitory factor. PLos One2009, 4: e6724.
  33. Huang J, Chen T, Liu X, Jiang J, Jinsong Li, Li D, Liu X, Li W, Kang J& Pei G. More synergetic cooperation of Yamanaka factors in induced pluripotent stem cells than in embryonic stem cells. Cell Res2009, 19: 1127-1138.
  34. LiJinsong& Mombaerts P. Nuclear transfer-mediated rescue of the nuclear genome of nonviable mouse cells frozen without cryoprotectant. Biol Reprod 2008 79(4):588-593.
  35. Li Jinsong#, Guasch G#, Greco V#, Fuchs E* & Mombaerts P*. Cloned mice from Skin Stem Cells.Proc Natl Acad Sci USA 2007, 104(8): 2738-2743.
  36. LiJinsong,Ishii T, Wen D& Mombaerts P. Non-equivalence of cloned and clonal mice. Current Biology2005, 15(18): R756-R757.
  37. LiJinsong, IshiiT, FeinsteinP&Mombaerts P. Odorant receptor gene choice is reset by nuclear transfer from mouse olfactory sensory neurons. Nature 2004, 428: 393-398.
  38. Han Z, Chen D, Li Jinsong, Sun Q, Wan Q, Kou Z, Rao G, Lei L, Liu Z & Fang S. Mitochondrial DNA heteroplasmy in calves cloned by using adult somatic cell. Mol Reprod Dev2004, 67(2): 207-214
  39. Chen D#, Li Jinsong#, Han Z, Lei L, Liu Z, Kou Z, Ma S, Du Q & Sun Q. Somatic cell bovine cloning: efficiency of donor cells from femaleand male using different recipient cows. Chinese Science Bulletin 2003, 48(6): 549-554.
  40. Zhu Z, Chen D, Li Jinsong, Lian L, Lei L, Han Z & Sun Q. Rotation of meiotic spindle is controlled by microfilaments in mouse oocytes. Biology of Reproduction 2003, 68: 943-946.
  41. Han Z, Chen D, Li Jinsong, Sun Q, Wang P, Du J & Zhang H. Flow cytometric cell-cycle analysis of cultured fibroblasts from the giant panda, Ailuropoda melanoleuca L. Cell Biol Int 2003, 27(4): 349-353
  42. Wen D, Yang C, Cheng Y, Li Jinsong, Liu Z, Sun Q, Zhang J, Lei L, Wu Y, Kou Z &Chen D. Comparison of developmental capacity for intra- and interspecies cloned cat (Felis catus) embryos. Mol Reprod Dev 2003, 66(1): 38-45
  43. Chen Y, He Z, Liu A, Wang K, Mao W, Chu J, Lu Y, Fang Z, Shi Y, Yang Q, Chen D, Wang M, Li Jinsong, Huang S, Kong X, Shi Y, Wang Z, Xia J, Long Z, Xue Z, Ding W & Sheng H. Embryonic stem cells generated by nuclear transfer of human somatic nuclei into rabbit oocytes. Cell Res2003, 13(4): 251-263.
  44. Li Jinsong, Chen D, Han Z, Zhu Z, Wen D, Liu Z, Wang M, Lian L, Du J, Wang P& Zhang H. Serial Nuclear Transfer Improves the Development of Interspecies Reconstructed Giant Panda Embryos. Chinese Science Bulletin2002, 47(6):467-469
  45. Chen D, Wen D, Zhang Y, Sun Q, Han Z, Liu Z, Shi P, Li Jinsong, Xianyu J, Lian L, Kou Z, Wu Y, Chen Y, Wang P& Zhang H. Interspeices implantation and mitochondria fate of panda-rabbit cloned embryos. Biol Reprod 2002,67:637-642.
  46. Han Z, Chen D, Li Jinsong, Sun Q, Wang P, Huang Y & Du J. The culture of fibroblasts from diaphragm of Giant Panda. In Vitro Cell Dev Biol 2001, 37:644-645
  47. Li G, Chen D, Lian L, Sun Q, Wang M, Liu J, Li Jinsong& Han Z. Viable rabbits derived from reconstructed oocytes by germinal vesicle transfer after intracytoplamic sperm injection (ICSI). Mol Reprod Dev2001, 58:180-185
  48. Ding B, Shi P, Xianyu J, Zhang Y, Chen D, Sun Q, Li G, Wang M, Liu J, Han Z, Song X, Li Jinsong& Chen Y. Microsatellite DNA analysis prove nucleus of interspecies reconstructed blastocyst coming from that of donor giant panda. Chinese Science Bulletin 2000, 45(20):1883-1885
  49. Liu J, Wang M, Lian L, Li jinsong, Gao S, Han Z, Sun Q, Song X, Zhang D, Li Y, Xu Z &Chen D. Nuclear Transfer Using Nonquiescent Adult Fibroblasts from a Bovine Ear. Chinese Science Bulletin1999, 44(21): 1971-1974
  50. Chen D, Sun Q, Liu J, Li G, Lian L, Wang M, Han Z, Song X, Li Jinsong, Sun Q, Chen Y, Zhang Y & Ding B. The Giant Panda Somatic Nucleus can dedifferentiate in Rabbit Ooplasm and Support Early Development of the Reconstructed Egg. Science in China 1999, 42(4): 346-353

Education Background & Academic Experience
2002-2007: Postdoctoral Fellow, The Rockefeller University
1999-2002: Ph.D., Institute of Zoology, Chinese Academy of Sciences
1993-1996: M Sc, Yangzhou University
1989-1993: B.S., Jiangxi Agriculture University

Research Team

 

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