NIBS 北京生命科学研究所

高绍荣

高绍荣博士

北京生命科学研究所研究员

Shaorong Gao, Ph.D.
Assistant Investigator, NIBS, Beijing, China

Phone：010-80726688
Fax： 010-80726689
E-mail：gaoshaorong@nibs.ac.cn

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 China Agricultural 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

2005-Present	中国北京生命科学研究所研究员
	Assistant Investigator at 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：

本实验室工作主要集中在研究哺乳动物体细胞克隆胚胎发育过程中再编程(Reprogramming)的分子机理。将体细胞核通过显微操作移入去除遗传物质的成熟卵母细胞中从而启动胚胎发育是一个由体细胞基因表达逆转进入胚胎细胞基因表达的再编程过程，正是由于我们对卵母细胞再编程的分子机理不清楚才使克隆成功的效率仍然处于非常低的水平。而能够分离纯化卵母细胞中特有的再编程因子(Reprogramming Factors) 将会对克隆效率的提高以及干细胞的研究起到十分重要的意义。我们今后工作重点之一就是要通过核移植并结合生物化学的方法鉴定卵母细胞胞质中的这些重要因子。

近来，人们已经意识到胚胎干细胞的研究对一些疾病治疗的重大前景。通过核移植的方法可以得到与病人遗传信息相同的胚胎干细胞，从而可以消除移植后免疫排斥的可能。我们实验室已经通过核移植的方法建立起了数十株小鼠体细胞克隆胚胎干细胞系并正在进行体外分化为心肌组织的研究和体内移植后功能的鉴定。同时我们正在进行人治疗性克隆的研究以期尽快建立病人来源的体细胞核移植胚胎干细胞系。

小鼠胚胎发育过程中卵母细胞与早期胚胎极性发生机理的研究也是我们实验室的重要研究方向。

因此，本实验室以后的工作主要集中在：

1.	研究克隆胚胎再编程(Reprogramming)的分子机理，鉴定与纯化卵母细胞中特有的再编程因子(Reprogramming factor)。
2.	建立克隆胚胎干细胞系并进行体外分化与功能的研究。
3.	小鼠卵母细胞与早期胚胎极性发生机理的研究。

Research Description:

Our long-term goal is to understand the molecular mechanism of reprogramming during development of cloned embryos. The cloning efficiency remains very low with only 1-5% of cloned embryos can develop into offspring and the molecular mechanism of reprogramming of somatic cell genome remains unknown. We would be able to improve the cloning efficiency dramatically once the reprogramming factors present in the oocyte can be characterized, and it would be able to advance the stem cell research as well. Our long-term aim is to define the factors present in the oocyte cytoplasm that are responsible for reprogramming of somatic cell genome after somatic cell nuclear transfer.

Recently, embryonic stem cells are proposed as promising for therapeutic purpose. The ES cells derived from the SCNT embryos reconstructed using the somatic cells from the specific patient would be able to eliminate the possibility of immune rejection after engraftment. We have established over 100 somatic cell nuclear transfer ES (ntES) cell lines using the donor cells from different mouse strains and are carrying out the study on differentiation and functional research on the ntES cells in vitro. Meanwhile, we are trying to generate ntES cell lines using patient-specific somatic cells for further regenerative medicine research.

Molecular mechanism of asymmetric division in mouse oocytes during meiotic maturation and embryonic polarity occurred during early embryo development is another ongoing project in our laboratory.

Overall, our research will focus on:

1.	Understanding the molecular mechanism of reprogramming and define the reprogramming factors present in oocyte cytoplasm that are responsible for reprogramming of somatic cell genome.
2.	Establishing ntES cell lines and studying the differentiation and function of the ntES cells in vitro.
3.	Mechanism of oocyte and embryo polarity.

Publications:

1.

Wang S, Hu J, Guo X, Liu J.X. and Gao S (2008). ADP-ribosylation factor 1 regulates asymmetric cell division in female meiosis in mouse. Biol. Reprod. (in press)

2.

Chang G, Liu S, Wang F, Kou Z, Zhang Y, Chen D and Gao S (2008). Differential methylation status of imprinted genes in nuclear transfer derived ES (NT-ES) cells. Genomics Oct 20 [Epub ahead of print]

3.

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. 2008 Oct 1. [Epub ahead of print]

4.

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.

5.

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.

6.

Yang X, Cheng T, Sung LY, Gao S, Shen H, Yu H, Song Y, Smith SL, Tuck DP, Inoue K, Weissman SM (2007) Reply to “On the cloning of animals from terminally differentiated cells”. Nat. Genet. 39(2):137-138.

7.

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

8.

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.

9.

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)

10.

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

11.

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.

12.

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.

13.

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. Genetics 170(1):327-334.

14.

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.

15.

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 of Om locus polarity in cloned mouse embryos. Biol. Reprod. 72:487-491.

16.

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.

17.

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.

18.

Gao S and Latham KE (2004) Maternal and environmental factors in early cloned embryo development. Cytogenetic and Genome Research 105:279-284.

19.

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.

20.

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.

21.

Gao S (2004) Nuclear transfer with murine embryonic stem cells. In: gene targeting and Embryonic Stem Cells (Advanced methods). (Eds: Jim McWhir and Alison Thomas). Published by BIOS Scientific Publishers (Taylor & Francis Group). P23-43.

22.

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

23.

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.

24.

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.

25.

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.

26.

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.

27.

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.