国家蛋白质科学
中心•上海(筹)

分子生物学国
家重点实验室

细胞生物学国
家重点实验室

上海市分子男
科学重点实验室

中国科学院系统
生物学重点实验室
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院士风采
千人计划
杰出青年
青年千人
百人计划
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地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibs.ac.cn

全所PI名录 >

 
李劲松
研究员,课题组长,博士生导师
电话:54921422
E-mail: jsli@@sibcb.ac.cn

个人简介:
  

        1993年7月毕业于江西农业大学畜牧兽医系,获理学学士学位;1996年7月毕业于扬州大学畜牧兽医学院,获理学硕士学位;2002年7月毕业于中国科学院动物研究所,获理学博士学位;2002年8月至2007年7月在美国洛克菲勒大学从事博士后研究;2007年8月起任中科院上海生科院生物化学与细胞生物学研究所研究员,研究组长。2008年获“百人计划”项目支持,2012年获“杰出青年基金”支持。入选“2013年中青年科技创新领军人才”。

研究方向:细胞重编程与胚胎发育

研究工作:
  

        细胞重编程(cellular reprogramming)指的是细胞在特定的条件下被逆转恢复到全能性状态或多能性状态,或者形成多能干细胞系,或者进一步发育成一个新的个体的过程。核移植与诱导多能干细胞(induced pluripotent stem cell, iPSC)技术是两种主要的重编程方法。然而这两种技术都还很不成熟,存在效率很低、重编程细胞发育能力差、重编程的机制不清楚等问题。
        2012年,研究组建立了来自小鼠精子的孤雄单倍体胚胎干细胞,并证明这些细胞能够代替精子使卵母细胞“受精”产生半克隆小鼠(称为“半克隆”技术)。然而,半克隆技术不成熟,半克隆小鼠出生率低(4%左右),而且有一半的半克隆小鼠存在发育缺陷问题。2015年,研究组获得了能稳定高效产生半克隆小鼠的“类精子细胞”的单倍体干细胞(出生效率达到20%左右),并证明这些细胞能携带CRISPR-Cas9文库一步获得大量携带不同突变的小鼠,为实现小鼠个体水平的遗传筛选奠定了基础:
        本实验室开展以下几方面的研究:
        完善核移植及iPSC技术诱导细胞重编程的方法,提高重编程的效率;
        1. 探讨重编程细胞发育缺陷相关的分子机制,提高重编程细胞的质量;
        2. 探讨半克隆小鼠发育缺陷的相关分子机制,揭示与胚胎发育相关的重要机制;
        3. 结合“类精子细胞”的单倍体干细胞与CRISPR-Cas9技术,开展新的基因编辑应用研究;
        4. 开展CRISPR-Cas9技术介导的基因治疗研究。

代表性论文:

  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

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