dcbox小金库(中国)

高绍荣 博士

北京科学生命dcbox小金库(中国)高级研究员

Shaorong Gao, Ph.D.

Associate Investigator, NIBS, Beijing, China

教育经历

Education

工作经历

Professional Experience

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。我们主要顺利获得体细胞核移植(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取得多能干细胞。最近我们在世界上首次取得了由可诱导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 dcbox小金库(中国) reprogramming mediated by either somatic dcbox小金库(中国) nuclear transfer (SCNT) or over-expression of defined transcription factors which are highly enriched in the embryonic stem dcbox小金库(中国)s (ESCs). By using an inducible iPS system, we are trying to explore the molecular events governing the dcbox小金库(中国) fate conversion. Recently, we have proved the full pluripotency of iPS dcbox小金库(中国)s 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 dcbox小金库(中国)s are proposed as promising for therapeutic purpose. We have successfully established patient specific induced pluripotent stem dcbox小金库(中国)s (iPSCs) by over-expressing defined transcription factors. We are performing in vitro differentiation studies and further exploring the feasibilities of utilizing these dcbox小金库(中国)s clinically.

Overall, our research will focus on:

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 dcbox小金库(中国)s into pluripotent stem dcbox小金库(中国)s by Oct4. Stem dcbox小金库(中国)s 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) dcbox小金库(中国)s through tetraploid complementation. dcbox小金库(中国) 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-dcbox小金库(中国)-nuclear-transferred embryonic stem dcbox小金库(中国)s improve myocardial performance in infarcted rat heart. J dcbox小金库(中国) 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 dcbox小金库(中国)s (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 dcbox小金库(中国)-derived pluripotent stem dcbox小金库(中国)s. 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 dcbox小金库(中国) nuclear transfer- and fertilization-derived mouse embryonic stem dcbox小金库(中国)s 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 dcbox小金库(中国)s Using Spermatogenic dcbox小金库(中国)s. Stem dcbox小金库(中国)s 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 dcbox小金库(中国) Processing Components and Its Dominant Negative Mutant Caused Two-dcbox小金库(中国) 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 dcbox小金库(中国)s. Stem dcbox小金库(中国)s Dev. 19(1):53-60.

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

14. Zhang M, Wang F, Kou Z, Zhang Y, Gao S (2009) Defective chromatin structure in somatic dcbox小金库(中国) 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 dcbox小金库(中国)s 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. dcbox小金库(中国) Research 19(7):838-48.

17. Wang Y, Jiang Y, Liu S, Sun X, Gao S (2009) Generation of induced pluripotent stem dcbox小金库(中国)s from human beta-thalassemia fibroblast dcbox小金库(中国)s. dcbox小金库(中国) 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 dcbox小金库(中国)s into functional hematopoietic dcbox小金库(中国)s. 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 dcbox小金库(中国) 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) dcbox小金库(中国)s. 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 dcbox小金库(中国)s into cardiomyocytes. Cloning Stem dcbox小金库(中国)s 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 dcbox小金库(中国) 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 dcbox小金库(中国) cycles. Dev. Biol. 304:75-89.

26. Latham KE, Gao S, Han Z (2007) Somatic dcbox小金库(中国) 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 dcbox小金库(中国)s are more efficient than adult stem dcbox小金库(中国)s for cloning by somatic dcbox小金库(中国) 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 dcbox小金库(中国) 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 dcbox小金库(中国) 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 dcbox小金库(中国) 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 dcbox小金库(中国)s. 5:287-294. (Corresponding author)

40. Gao S, Chung YG, Williams JW, Riley J, Moley K, Latham KE. (2003) Somatic dcbox小金库(中国)-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 dcbox小金库(中国) 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 dcbox小金库(中国) confluence on production of clone mice using an inbred embryonic stem dcbox小金库(中国) 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.