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徐成冉


徐成冉

 

电子邮件: cxu(at)pku(dot)edu(dot)cn

电话: 010-62755513

实验室主页:

 

研究方向:

 

本实验室主要兴趣在于:

干细胞生物学:胚胎干细胞定向分化;组织器官再生。
发育生物学:哺乳动物肝脏和胰腺发育机理。
系统生物学:细胞信号、表观遗传对发育和再生过程中基因网络的调控。

 

哺乳动物中肝脏及胰腺相互协调在代谢的过程中发挥关键作用。在胚胎发育的早期,胰腺和肝脏的祖细胞从前肠内胚层的一个多能细胞区域竞争性起源,这个过程受到一些共同的细胞信号和转录因子调控。当肝脏和胰腺的细胞出现损伤和功能紊乱时,就会导致许多代谢疾病(如糖尿病,胰腺炎,肝炎等),严重影响健康。因此如何促进肝脏和胰腺的再生是本领域的重要问题。干细胞研究和肝脏、胰腺发育的调控相结合,将更好地解决这一问题。


本实验室长期研究方向主要集中在肝脏及胰腺发育过程中细胞分化,器官建成和再生,主要包括,(1)研究哺乳动物从胚胎发生开始的发育过程中肝实质细胞及内分泌细胞的分化及成熟机制。细胞信号、表观遗传修饰和基因网络协调作用,对这些细胞的分化及成熟过程进行着严格的调控。这些不同层次的调控机制是我们关注的重点。(2)利用获得的肝脏发育过程中的线索指导体外胚胎干细胞分化成成熟的肝实质细胞,用于对肝病进行细胞水平的治疗。(3)将胰腺发育中内分泌细胞分化和成熟过程中获得线索应用于干细胞分化为β细胞的流程,以更好的诱导出有生理功能、成熟的分泌胰岛素的β细胞。(4)通过对肝脏和胰腺发育过程的分子机制研究,结合体外干细胞诱导分化,体外重建有功能的肝脏和胰岛,为再生医疗治疗代谢疾病奠定基础。

 

代表性科研论文: 

 *corresponding author; #contribute equally 

1. Xin-Xin Yu#, Wei-Lin Qiu#, Liu Yang#, Yan-Chun Wang#, Mao-Yang He, Dan Wang, Yu Zhang, Lin-Chen Li, Jing Zhang, and Yi Wang and Cheng-Ran Xu*, Sequential progenitor states mark the generation of pancreatic endocrine lineages in mice and humans. Cell Research, doi: 10.1038/s41422-021-00486-w (2021)

2. Lin-Chen Li#, Xin Wang#, Zi-Ran Xu#, Yan-Chun Wang#, Ye Feng, Liu Yang, Wei-Lin Qiu, Li Yang, Xin-Xin Yu, Jun Gu and Cheng-Ran Xu*, Single-cell patterning and axis characterization in the murine and human definitive endoderm. Cell Research, 31(3):326-344 (2021).

3. Jaesung P Choi# , Xi Yang#, Shuang He, Renhua Song, Zi-Ran Xu, Matthew Foley, Justin J-L Wong, Cheng-Ran Xu, Xiangjian Zheng*, CCM2L (Cerebral Cavernous Malformation 2 Like) Deletion Aggravates Cerebral Cavernous Malformation Through Map3k3-KLF Signaling Pathway. Stroke, doi: 10.1161/STROKEAHA.120.031523 (2021)

4. Sisi Feng#, Jiaying Wu#, Wei-Lin Qiu#, Li Yang#, Xiaogang Deng#, Ying Zhou, Yabin Chen, Xiao Li, Lei Yu, Zi-Ran Xu, Yini Xiao, Xiongzhao Ren, Ludi Zhang, Chenhua Wang, Xiaoyan Ding, Yuelei Chen, Paul Gadue, Guoyu Pan, Mina Ogawa, Shinichiro Ogawa, Jie Na, Lijian Hui, Hao Yin*, Luonan Chen*, Cheng-Ran Xu* and Xin Cheng*, Large-scale generation of functional and transplantable hepatocytes and cholangiocytes from human endoderm stem cells. Cell Reports, 33(10):108455 (2020).

5. Xin Wang#, Li Yang#, Yan-Chun Wang#, Zi-Ran Xu, Ye Feng, Jing Zhang, Yi Wang and Cheng-Ran Xu*, Comparative analysis of cell lineage differentiation during hepatogenesis in humans and mice at the single-cell transcriptome level. Cell Research, 30(12):1109-1126 (2020) 

6. Xin-Xin Yu and Cheng-Ran Xu*, Understanding generation and regeneration of pancreatic β cells from a single-cell perspective (Review). Development, 12;147(7) :dev179051 (2020).

7. Ye Feng#, Wei-Lin Qiu#, Xin-Xin Yu, Yu Zhang, Mao-Yang He, Weiyi Zhang, Michael Franti, Junqing Ye*, Joerg D. Hoeck* and Cheng-Ran Xu*, Characterizing pancreatic β-cell heterogeneity in the streptozotocin model by single-cell transcriptomic analysis. Molecular Metabolism, 37:100982 (2020).

8. Xin-Xin Yu#, Wei-Lin Qiu#, Liu Yang, Yu Zhang, Mao-Yang He, Lin-Chen Li and Cheng-Ran Xu*, Defining multistep cell fate decision pathways during pancreatic development at single-cell resolution. The EMBO Journal, 15;38(8):e100164 (2019).

9. 杨李,拉毛切忠,徐成冉*,肝脏细胞分化和成熟的分子调控机制。中国细胞生物学学报,41(10):1853-1884 (2019).

10. Li Yang, Lin-Chen Li, Lamaoqiezhong, Xin Wang, Wei-Hua Wang, Yan-Chun Wang and Cheng-Ran Xu*, The contributions of mesoderm-derived cells in liver development. Seminars in Cell and Developmental Biology, 92:63-76 (2019).

11. Lin-Chen Li#, Wei-Lin Qiu#, Yu-Wei Zhang, Zi-Ran Xu, Yi-Ni Xiao, Caiying Hou, Lamaoqiezhong, Peng Yu, Xin Cheng and Cheng-Ran Xu*, Single-cell transcriptomic analyses reveal distinct dorsal/ventral pancreatic programs. EMBO Reports, 19(10):e46148 (2018).

12. Lin-Chen Li#, Xin-Xin Yu#, Yu-Wei Zhang#, Ye Feng#, Wei-Lin Qiu# and Cheng-Ran Xu*, Single-cell transcriptomic analyses of mouse pancreatic endocrine cells. Journal of Visualized Experiments, Sep 30;(139):58000 (2018).

13. Xin-Xin Yu#, Wei-Lin Qiu#, Liu Yang, Lin-Chen Li, Yu-Wei Zhang and Cheng-Ran Xu*, Dynamics of chromatin marks and the role of JMJD3 during pancreatic endocrine cell fate commitment. Development, 145(6):dev163162 (2018).

14. Li Yang#, Wei-Hua Wang#, Wei-Lin Qiu#, Zhen Guo, Erfei Bi and Cheng-Ran Xu*, A single-cell transcriptomic analysis reveals precise pathways and regulatory mechanisms underlying hepatoblast differentiation. Hepatology, 66(5):1387-1401 (2017).

15. Wei-Lin Qiu#, Yu-Wei Zhang#, Ye Feng#, Lin-Chen Li, Liu Yang and Cheng-Ran Xu*, Deciphering pancreatic islet β-cell and α-cell maturation pathways and characteristic features at the single-cell level. Cell Metabolism, 25:1194-1205 (2017).

16. Ramkumar Mohan, Yiping Mao, Shungang Zhang, Yuwei Zhang, Cheng-Ran Xu, Gérard Gradwohl and Xiaoqing Tang*. Differentially expressed microRNA-483 confers distinct functions in pancreatic beta- and alpha-cells. Journal of Biological Chemistry, 290(32): 19955-66 (2015).

17. Cheng-Ran Xu, Lin-Chen Li, Greg Donahue, Lei Ying, Yu-Wei Zhang, Paul Gadue & Kenneth S. Zaret*. Dynamics of Genomic H3K27me3 Domains and Role of EZH2 during Pancreatic Endocrine Specification. The EMBO Journal, 33(19): 2157-2170 (2014)

18. Cheng-Ran Xu & Kenneth S. Zaret*. Chromatin "Pre-Pattern" and Epigenetic Modulation in the Cell Fate Choice of Liver over Pancreas in the Endoderm. Review, Nucleus, 3(2): 150-154 (2012)

19. Cheng-Ran Xu, Philip A. Cole, Jay D. Kormish, Shannon Dent & Kenneth S. Zaret*. Chromatin "Pre-Pattern" and Histone Modifiers in a Fate Choice for Liver and Pancreas. Science, 332: 963-6 (2011)

20. Cheng-Ran Xu & Ann J. Feeney*. The epigenetic profile of Ig genes is dynamically regulated during B cell differentiation and is modulated by pre-B cell receptor signaling. Journal of Immunology, 182(3): 1362-9 (2009)

21. Cheng-Ran Xu, Lana Schaffer, Steven R. Head & Ann J. Feeney*. Reciprocal patterns of methylation of H3K27 and H3K36 on proximal vs. distal IgVH genes are modulated by IL7 and Pax5. The Proceedings of the National Academy of Sciences USA (PNAS), 105: 8685-8690 (2008)

22. Cheng-Ran Xu, Cui Liu, Yi-Lan Wang, Lin-Chen Li, Wen-Qian Chen, Zhi-Hong Xu & Shu-Nong Bai*. Histone acetylation affects expression of cellular patterning genes in the Arabidopsis root epidermis. The Proceedings of the National Academy of Sciences USA (PNAS), 102: 14469-14474 (2005)

 

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