精原干细胞研究组!
韩春生 研究员
生殖细胞形成和发育的基因调控
欢迎您加入精原干细胞研究组!
– 工作人员:林羲雯(生物信息学分析师,实验室主管)
– 研究生:谢丹,刘元,宋雪,贺伟,李亚欢,赵少康,闫琳,刘晓薇,胡帅涛,薛亚林,孙静, MD Alim, , Khan
动物的精子发生是指性腺中一小群叫做精原干细胞(SSCs)的细胞经过复杂的增殖、分化、减数分裂最终形成精子的过程。在胚胎发育早期,少数上胚层细胞首先形成原始生殖细胞,这些早期的生殖细胞经过增殖、迁徙和分化最终形成了SSCs。SSCs不仅能够经过分化变为能进行减数分裂的精母细胞,而且还能够重编程形成多能性干细胞。因此,SSCs是研究干细胞自我更新、分化、去分化、以及减数分裂的优秀细胞模型。精子发生的缺陷会导致男性不育和出生缺陷,而对其进行干预则可能发展出避孕、不育治疗、出生缺陷矫正、动物繁育、再生医学等方面的新技术。我们目前正在利用分子生物学、小鼠基因敲除、高通量组学和生物信息学等技术来研究SSCs增殖、分化、重编程以及利用多能性干细胞获得生殖细胞的分子机理。
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BEND2 is a key of , gene ,and state mouse .
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研究内容和目标:
1. 精原干细胞(SSCs)增殖、分化(减数分裂)以及去分化(重编程)研究。我们已经建立了精原干细胞的体外培养扩增以及多能性干细胞诱导形成生殖细胞的平台,为发展基于人工诱导生殖细胞的不育治疗技术奠定了基础。未来将面向男性不育治疗的应用目标,快速推进在体外获得“人造”精子的工作。
2. 精子发生的表观遗传调控机理。我们已经利用分离纯化的多种生精细胞结合组学技术,在DNA、RNA、蛋白质三个水平绘制哺乳动物精子发生基因调控的全局视图,利用基因敲除和分子生物学技术重点研究关键转录因子在精子发生中的功能,为男性不育的诊断提供了候选基因。未来我们将继续利用组学技术研究在生殖细胞形成和发育过程中基因表观遗传修饰的变化以及RNA和蛋白质的表达变化,发现对分化起关键作用的基因,并针对其作用机理设计出更加有效的体外分化诱导方案,为临床转化奠定基础。
代表性发表论文:
Ning Y, Duo S, Lin X, Zhang H, Fei J, Zhang B, Zeng Y, Xie D, Chen J, Liu X, Han C*. PBX4 limb and in mice. Cell . 2024 Jan 17:. doi: 10.1111/cpr.13580. Epub ahead of print. PMID: .Li J, Lin X, Xie L, Zhao J, Han C*, Deng H*, Xu J*,A /Cas9-based ErbB as a new of human naïve and ,Life , 2023, , Ma, L., Xie, D., Luo, M., Lin, X., Nie, H., Chen, J., Gao, C., Duo, S., and Han, C. (2022) and of BEND2 as a key of mouse . , 8(21):.Chen, J., Gao, C., Luo, M., Zheng, C., Lin, X., Ning, Y., Ma, L., He, W., Xie, D., Liu, K., Hong, K., Han, C. (2022) -202 by – REC8 . EMBO , 17;.Chen, J., Gao, C., Lin, X., Ning, Y., He, W., Zheng, C., Zhang, D., Yan, L., Jiang, B., Zhao, Y., , MA., Han, C. (2021) The miR-202 and mouse ., 148(24)Zheng ,C., , Y., Jiang, B., Lin, X., Chen, J., Dong, M., , X., Yuan, S., Sun, Q., Han, C. (2019) Non- RNA is for sperm head and in mice. Biol , 100(6):1673-, D., Xie, D., Lin, X., Ma, L., Chen, J., Wang, Y., Duo, S., Feng, Y., Zheng, C., Jiang, B., Ning, Y., Han, C.(2018) The SOX30 is a key of mouse . ,145. doi: 10.1242/dev..Feng, Y., Ning, Y., Lin, X., Zhang, D., Liao, S., Zheng, C., Chen J., Wang Y., Ma L., Xie D., Han C.(2018) p53- Stem Cells Into State by Nanog. Stem Cells Dev, 27:692-703.Hu, X., Shen, B., Liao, S., Ning, Y., Ma, L., Chen, J., Lin, X., Zhang, D., Li, Z., Zheng, C., Feng, Y., Huang, X., Han C.(2017) Gene of Zmym3 in mice at with in .Cell Death Di, 8:e2910.Chen, J., Cai, T., Zheng, C., Lin, X., Wang, G., Liao, S., Wang, X., Gan, H., Zhang, D., Hu, X., Wang, S., Li, Z., Feng, Y., Yang, F., and Han, C. (2017) -202 stem cells by cell cycle , Acids Res. 45(7):4142-4157.Tu, Z., , M. B., Liu, H., Zhang, J., , K., Risal, S., Shao, J., , A., , V., , L., Singh, M., Zheng, C., Han, C., Chen, Z., , P., , J. A., and Liu, K. (2017) A-Cdk2 – I of Cdk2 , Proc Natl Acad Sci U S A, 114:592-, M., Zhang, L., Cui, X., Lin, X., Li, Y., Wang, Y., Wang, Y., Qin, Y., Chen, D., Han, C., Zhou, B., Huff, V., and Gao, F. (2017) Wt1 the of and cells by Sf1 , , 44-, S., Wang, X., Ma, L., Lin, X., Zhang, D., Li, Z., Wu, Y., Zheng, C., Feng, X., Liao, S., Feng, Y., Chen, J., Hu, X., Wang, M., and Han, C. (2016) Acid Is for the In Vitro of Mouse , Stem 7, 80-94.Lin, X., Han, M., Cheng, L., Chen, J., Zhang, Z., Shen, T., Wang, M., Wen, B., Ni, T., and Han, C. (2016) , , and of in mouse cells, RNA 13,1011-1024.Wu, Y., Hu, X., Li, Z., Wang, M., Li, S., Wang, X., Lin, X., Liao, S., Zhang, Z., Feng, X., Wang, S., Cui, X., Wang, Y., Gao, F., Hess, R. A., and Han, C. (2016) RFX2 Is a Key of Mouse , 6, 20435.Yang, Y., Feng, Y., Feng, X., Liao, S., Wang, X., Gan, H., Wang, L., Lin, X., and Han, C. (2016) BMP4 with Acid to the of in Mouse , Stem cells , .Xue, Y., , E. W., Ye, K., Zhang, K., Chang, S., Wang, X., Wu, J., Gao, G., Zhao, F., Li, J., Han, C., Xu, S., Xiao, J., Yang, X., Ying, X., Zhang, X., Chen, W. H., Liu, Y., Zhang, Z., Huang, K., and Yu, J. (2016) :What Are We ?, , & 14, 253-261.Gao, Y., Bai, X., Zhang, D., Han, C., Yuan, J., Liu, W., Cao, X., Chen, Z., , F., Zhu, Z., Gao, F., and Qin, Y. (2016) 4 for , & 23, 441-449.#Zhu, L., #Han, C. S., Cao, Z. L., Wang, Z. B., Han, R. G., Wang, B., and Sun, Q. Y. (2015) of the and of in vitro- from Types of Ovary , and 80, 179-186.Wang S.,Wang Xx.,Wu Yj., and *Han, C. (2015) ,IGF-1R Is for the of Mouse Stem Cells by the G2/M of the Cell Cycle,Stem Cells and 24,471-483。
Li, Y., Wang, X., Feng, X., Liao, S., Zhang, D., Cui, X., Gao, F., and *Han, C. (2014) of male germ cells from mouse stem cells in vitro, Stem Cell Res 12, 517-530.*Han, C. (2014) ,Which one is the real for the pair?,Asian of 16,667-668。Gan, H., Wen, L., Liao, S., Lin, X., Ma, T., Liu, J., Song, C.-x., Wang, M., He, C., *Han, C., and *Tang, F. (2013) of 5-e mouse , 4, 1995.Wang, F., Yang, Y., Lin, X., Wang, J. Q., Wu, Y. S., Xie, W., Wang, D., Zhu, S., Liao, Y. Q., Sun, Q., Yang, Y. G., *Guo, C., *Han, C., and *Tang, T. S. (2013) -wide Loss of 5-hmC is a Novel of ‘s ,Human 22, 3641-3653.Wu, Y., Liao, S., Wang, X., Wang, S., Wang, M., and *Han, C. (2013) BNC1 by BNC1 to the , FEBS 587, 2099-2104.hi, Y., , X., Xu, B., Hua, J., Liao, S., Shi, Q., *Cooke, H. J., *Han, C. (2013) SYCP3-like X- 2 is in germ cells and with 2 and 60, Gene 527, 352-359.Gan, H., Cai, T., Lin, X., Wu, Y., Wang, X., *Yang, F., and *Han, C. (2013) and Post- of Mouse , Mol Cell 12, 1144-1157.Hou, X., Zhang, W., Xiao, Z., Gan, H., Lin, X., Liao, S., and *Han, C. (2012) and of E3 in the mouse , BMC 13, 495.Zhang, Y., Wang, S., Wang, X., Liao, S., Wu, Y., and *Han, C. (2012) FGF2 is for the and of mouse stem cells, Cell 22, 773-776.Gan, H., Lin, X., Zhang, Z., Zhang, W., Liao, S., Wang, L., and *Han, C. (2011) piRNA of mouse , RNA 17, 1191-1203.
