高绍荣博士 - 科学研究 - 北京生命科学研究所

高绍荣博士

北京生命科学研究所高级研究员

Shaorong Gao, Ph.D.

Associate Investigator, NIBS, Beijing, China

教育经历

Education

1993	中国山东农业大学动物科技学院学士
	B.S. Department of Animal Science and Technology,Shandong Agricultural University, Tai’an, China
1996	中国农业大学动物科技学院生殖生物学硕士
	M.Sc Department of Animal Science and Technology of ChinaAgricultural University, Beijing, China
2000	中国科学院动物学研究所生殖生物学国家重点实验室生殖生物学博士
	PH.D. State Key Laboratory of Reproductive Biology,Institute of Zoology, Chinese Academy of Sciences, China

工作经历

Professional Experience

2011-2013	北京生命科学研究所高级研究员 Associate Investigator, National Institute of Biological Sciences, Beijing, China
2005-2011	北京生命科学研究所研究员
	Assistant Investigator, National Institute of Biological Sciences, Beijing, China
2004-2005	美国康涅狄格州大学助理教授
	Assistant Professor at University of Connecticut ,USA
2004	美国坦普尔大学医学院费尔斯肿瘤和分子生物学研究所助理科学家
	Associate Scientist at Fels Institute for Cancer Research and Molecular Biology , Temple University School of Medicine ,USA
2002-2004	美国坦普尔大学医学院费尔斯肿瘤和分子生物学研究所博士后
	Post-doctoral Scientist at Fels Institute for Cancer Research and Molecular Biology , Temple University School of Medicine , USA
2000-2002	英国苏格兰爱丁堡大学罗斯林研究所基因表达与发育系博士后
	Post-doctoral Scientist at Department of Gene Expression& Development of Roslin Institute, Britain
1998-2000	美国布朗大学医学院罗得岛州妇幼医院不孕不育科研究员助理
	Research Associate at Division of Reproductive Medicine and Infertility Women or Infants Hospital of Rhode Island, Brown University School of Medicine , USA

研究概述

Research Description

我们实验室工作主要集中在研究哺乳动物体细胞重编程(Reprogramming)的分子机理。我们主要通过体细胞核移植(SCNT)和在体细胞中过表达特定转录因子的方法(iPS)对分化的体细胞进行重编程从而获得多能干细胞。最近我们在世界上首次获得了由可诱导iPS细胞产生的四倍体互补小鼠，证明iPS细胞具有与正常ES细胞类似的真正多能性,被Times杂志评为2009年世界十大医学突破之一。我们的长期目标是理解两种体细胞重编程方法是如何将处于高度分化的体细胞命运逆转。

近来，人们已经意识到胚胎干细胞的研究对于一些疾病的治愈具有美好的前景。我们已经成功建立起病人特异的iPS细胞系并且正在集中研究这些病人特异的iPS细胞系的应用前景。

因此，本实验室以后的工作主要集中在：

1.研究体细胞重编程(Reprogramming)的分子机理，理解细胞分化与重编程的调控机制。

2.建立病人特异诱导多能干细胞系并进行体外分化与功能的研究。

Our long-term goal is to understand the molecular mechanism of somatic cell reprogramming mediated by either somatic cell nuclear transfer (SCNT) or over-expression of defined transcription factors which are highly enriched in the embryonic stem cells (ESCs). By using an inducible iPS system, we are trying to explore the molecular events governing the cell fate conversion. Recently, we have proved the full pluripotency of iPS cells through tetraploid complementation and this achievement has been selected by Times as one of the top ten medical breakthroughs worldwide in 2009. Meanwhile, we are trying to understand the role of specific proteins identified in oocytes in the process of reprogramming.

Recently, embryonic stem cells are proposed as promising for therapeutic purpose. We have successfully established patient specific induced pluripotent stem cells (iPSCs) by over-expressing defined transcription factors. We are performing in vitro differentiation studies and further exploring the feasibilities of utilizing these cells clinically.

Overall, our research will focus on:

1.	Understanding the molecular mechanism of somatic cellreprogramming mediated by SCNT and iPS approaches.
2.	Establishment of patient specific pluripotent stem cell lines and further investigating the clinical application of these reprogrammed cells.

Publications:

1. Wu T., Wang H., He J., Kang L., Jiang Y., Liu J., Zhang Y., Kou Z., Liu L., Zhang X., Gao S. (2011) Reprogramming of trophoblast stem cells into pluripotent stem cells by Oct4. Stem Cells 2011 Feb 8. [Epub ahead of print].

2. Kang L., Wu T., Tao Y., Yuan Y., He J., Zhang Y., Luo T., Kou Z., Gao S.(2010) Viable mice produced from 3-factor induced pluripotent stem (iPS) cells through tetraploid complementation. Cell Research 2010 Nov 30. [Epub ahead of print].

3. Wang S., Kou Z., Jing Z., Zhang Y., Guo X., Dong M., Wilmut I., Gao S.(2010) Proteome of mouse oocytes at different developmental stages.Proc. Natl. Acad. Sci. USA 107(41):17639-44.

4. Hu J, Wang F, Yuan Y, Zhu X, Wang Y, Zhang Y, Kou Z, Wang S, Gao S.(2010) The novel importin-alpha family member Kpna7, is required for normal fertility and fecundity in the mouse. J. Biol. Chem.285(43):33113-22.

5. Lü S, Li Y, Liu S, Wang H, He W, Zhou J, Liu Z, Zhang Y, Lin Q, Duan C, Yang X, Gao S, Wang C. Engineered heart tissue graft derived from somatic-cell-nuclear-transferred embryonic stem cells improve myocardial performance in infarcted rat heart. J Cell Mol Med. 2010 Jun 25. [Epub ahead of print]. (co-correspondence)

6. Kou Z., Kang L., Yuan Y., Tao Y., Zhang Y., Wu T., He J., Wang J., Liu Z., Gao S.. (2010) Mice cloned from induced pluripotent stem cells (iPSCs). Biol. Reprod. 83:238-243.

7. Chang G., Miao YL., Zhang Y., Liu S., Kou Z., Chen DY., Sun QY., Gao S..(2010) Linking incomplete reprogramming to the improved pluripotency of murine embryonal carcinoma cell-derived pluripotent stem cells. PLoS One. 26;5(4):e10320.

8. Lü S, Wang H, Lu W, Liu S, Lin Q, Li D, Duan C, Hao T, Zhou J, Wang Y, Gao S, Wang C.. (2010) Both the transplantation of somatic cell nuclear transfer- and fertilization-derived mouse embryonic stem cells with temperature-responsive chitosan hydrogel improve myocardial performance in infarcted rat hearts. Tissue Eng Part A. 16(4):1303-15. (co-correspondence)

9. Zhao Q, Wang J, Zhang Y, Kou Z, Liu S and Gao S. (2010) Generation of Histocompatible Androgenetic Embryonic Stem Cells Using Spermatogenic Cells. Stem Cells 2010; 28(2):229-239.

10. Hu J, Wang F, Zhu X, Yuan Y, Ding M and Gao S. (2010) Mouse ZAR1-like (XM_359149) Colocalizes with mRNA Processing Components and Its Dominant Negative Mutant Caused Two-cell Stage Embryonic Arrest. Dev. Dyn. 2010; 239(2):407-24.

11. Wang J, Zhang M, Zhang Y, Kou Z, Han Z, Chen DY, Sun QY, Gao S.(2010) The histone demethylase JMJD2C is stage-specifically expressed in preimplantation mouse embryos and is required for embryonic development. Biol. Reprod. 82(1):105-11.

12. Gao Y, Wang B, Xiao Z, Chen B, Han J, Wang X, Zhang JJ, Gao S, Zhao Y, Dai J. (2010) Nogo-66 regulates Nanog expression through Stat3 pathway in murine embryonic stem cells. Stem Cells Dev. 19(1):53-60.

13. Kang L, Wang J, Zhang Y, Kou Z, Gao S (2009) iPS cells can support full term development of tetraploid blastocyst-complemented embryos. Cell Stem Cell 5(2):135-138.

14. Zhang M, Wang F, Kou Z, Zhang Y, Gao S (2009) Defective chromatin structure in somatic cell cloned embryos. J. Biol. Chem. 284(37):24981-7.

15. Ding J, Guo Y, Liu S, Yan Y, Chang G, Kou Z, Zhang Y, Jiang Y, He F, Gao S(2009) ES Cells Derived from Somatic Cloned and Fertilized Blastocysts are Post-transcriptionally Indistinguishable: a MicroRNA and Protein Profile Comparison. Proteomics 9(10):2711-21.

16. Guo X and Gao S (2009) LGN regulates meiotic spindle organization, anchoring and involves in cortical polarization during mouse oocytes maturation. Cell Research 19(7):838-48.

17. Wang Y, Jiang Y, Liu S, Sun X, Gao S (2009) Generation of induced pluripotent stem cells from human beta-thalassemia fibroblast cells. Cell Research 19(9):1120-3.

18. Huang S, Wang J, Liu S, Li Y, Hu J, Kou Z, Zhang Y, Sun X, Gao S (2009)Differentiation of reprogrammed somatic cells into functional hematopoietic cells. Differentiation. 78(2-3):151-8.

19. Yao H, Li B, Wang S, Kou Z, Zhang Y, Gao S, Gou K. (2009) Genome-wide and gene specific paternal demethylation in androgenetic embryos. Front Biosci. 14:3884-91.

20. Wang S, Hu J, Guo X, Liu JX, Gao S (2009) ADP-ribosylation factor 1regulates asymmetric cell division in female meiosis in Mouse. Biol. Reprod. 80:555-562.

21. Chang G, Liu S, Wang F, Kou Z, Zhang Y, Chen D and Gao S (2009) Differential methylation status of imprinted genes in nuclear transfer derived ES (NT-ES) cells. Genomics 93(2):112-9.

22. Qin D, Gan Y, Shao K, Wang H, Li W, Wang T, He W, Xu J, Zhang Y, Kou Z,Zeng L, Sheng G, Esteban MA, Gao S, Pei D. (2008) Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. J Biol Chem. 283(48):33730-5.

23. Lv S, Liu S, He W, Duan C, Li Y, Liu Z, Hao T, Li J, Wang C and Gao S(2008) Bioreactor cultivation enhances NTEB formation and differentiation of NTES cells into cardiomyocytes. Cloning Stem Cells 10(3):363-370.

24. Wang F, Kou Z, Zhang Y and Gao S (2007) Dynamic reprogramming of histone acetylation and methylation in the first cell cycle of cloned mouse embryos. Biol. Reprod. 77:1007-1016.

25. Vassena R, Han Z, Gao S, Baldwin DA, Schultz RM, Latham KE (2007)Tough beginning: Alternations in the transcriptome of cloned embryos during first two cell cycles. Dev. Biol. 304:75-89.

26. Latham KE, Gao S, Han Z (2007) Somatic cell nuclei in cloning: strangers traveling in a foreign land. Adv. Exp. Med. Biol. 591:14-29.

27. Sung LY*, Gao S*, Shen H, Yu H, Song Y, Smith SL, Chang CC, Kuo L, Lian J, Tian XC, Tuck DP, Weissman SM, Yang X and Cheng T (2006) Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer. Nat. Genet. 38(11): 1323-1328. (* Co-first author)

28. Gao S (2006) Protocols for nuclear transfer in the mice. Methods in Molecular Biology , 325:25-33. (Corresponding author)

29. Chung YG, Gao S and Latham KE (2006) Optimization of procedures for cloning by somatic cell nuclear transfer in mice. Methods in Molecular Biology, 348: 111-124.

30. Miyara F, Han Z, Gao S, Vassena R and Latham KE (2006) Non-equivalence of embryonic and somatic cell nuclei affecting spindle formation in early cloned embryos. Dev. Biol. 289 (1):206-217.

31. Gao S, Han Z, Kihara M, Adashi E, and Latham KE (2005) Protease inhibitor MG132 in cloning: no end to the nightmare. Trends Biotechnol.23:66-68.

32. Gao S, Chung YG, Parseghian MH, King GJ, Adashi EY, Latham KE. (2004) Rapid H1 linker histone transitions following fertilization or somatic cell nuclear transfer: Evidence for a uniform development program in mice.Dev. Biol. 266(1):62-75.

33. Wu G, Hao L, Han Z, Gao S, Latham KE, de Villena F PM, Sapienza C. (2005) Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division. Genetics170(1):327-334.

34. Gao S, Wu G, Han Z, de la Casa-Esperon E, Sapienza C, and Latham KE (2005) Recapitulation of the Ovum mutant (Om) phenotype and loss ofOm locus polarity in cloned mouse embryos. Biol. Reprod. 72:487-491.

35. Nolen LD, Gao S, Han Z, Mann MR, Chung YG, Otte AP, Bartolomei MS and Latham KE (2005) X chromosome reactivation and regulation in cloned embryos. Dev. Biol. 279:525-540.

36. Han Z, Chung YG, Gao S, Latham KE (2005) The maternal genome governs the earliest effects of the embryonic genome on embryo phenotype. Biol. Reprod. 72:612-618.

37. Gao S and Latham KE (2004) Maternal and environmental factors in early cloned embryo development. Cytogenetic and Genome Research105:279-284.

38. Gao S, Czirr E, Chung YG, Han Z and Latham KE (2004) Genetic variation in oocyte phenotype revealed through parthenogenesis and cloning: Correlation with differences in pronuclear epigenetic modification. Biol. Reprod. 70:1162-1170.

39. Gao S, McGarry M, Latham KE and Wilmut I (2003) Cloning of mice by nuclear transfer. Cloning and Stem Cells. 5:287-294. (Corresponding author)

40. Gao S, Chung YG, Williams JW, Riley J, Moley K, Latham KE. (2003) Somatic cell-like features of cloned mouse embryos prepared with cultured myoblast nuclei. Biol. Reprod. 69:48-56.

41. Gao S, McGarry M, Ferrier T, Fletcher J, Harkness L, De Sousa P and Wilmut I. (2003) Effect of donor oocytes and culture conditions on development of cloned mice embryos. Mol. Reprod. Dev. 66:126-133.

42. Gasparrini B, Gao S, Ainslie A, Fletcher J, McGarry M, Ritchie WA, Springbett AJ, Overstrom EW, Wilmut I and De Sousa P. (2003) Cloned mice produced from embryonic stem cell karoplasts and activated cytoplasts prepared by induced enucleation. Biol. Reprod. 68: 1259-1266.

43. Gao S, McGarry M, Ferrier T, Pallante B, Priddle H, Gasparrini B, Fletcher J, Harkness L, De Sousa P, McWhir J and Wilmut I (2003) Effect of cell confluence on production of clone mice using an inbred embryonic stem cell line. Biol. Reprod. 68:595-603.

44. Gao S, Gasparrini B, McGarry M, Ferrier T, Fletcher J, Harkness L, De Sousa P and Wilmut I. (2002) Germinal vesicle material is essential for nuclear remodeling after nuclear transfer. Biol. Reprod. 67:928-934.