中心PI


 

徐成冉


电子邮件: cxu(at)pku(dot)edu(dot)cn

电话: 010-82805312

实验室主页:

研究方向:

本实验室聚焦于干细胞生物学、发育生物学与系统生物学的交叉研究,主要研究方向包括:

干细胞生物学:探索胚胎干细胞的定向分化机制及其在组织和器官再生中的应用。

发育生物学:解析哺乳动物肝脏和胰腺的发育机理,揭示细胞分化与器官建成的调控规律。

系统生物学:研究细胞信号与表观遗传对基因网络的整合调控,阐明其在发育与再生过程中的作用。

肝脏与胰腺是代谢调控的核心器官,二者在胚胎早期均源自前肠内胚层,其命运选择受多重信号通路与转录因子的精细控制。器官的功能紊乱可能导致糖尿病和肝病等重大疾病的发生。因此,阐明肝脏和胰腺的发育及再生机制,并推动再生医学的临床转化,是本领域的关键科学问题。

基于此,本实验室的长期研究目标为:

1)揭示肝实质细胞与胰腺内分泌细胞在胚胎发育和成熟过程中的机制,重点解析细胞信号、表观遗传调控及基因网络的协调作用;

2)借助发育规律指导胚胎干细胞体外分化为成熟肝细胞,为肝脏疾病的细胞治疗提供基础;

3)优化干细胞分化为功能性胰岛细胞的策略,获得具有生理功能的成熟类胰岛组织,对糖尿病进行细胞治疗;

4)研究肝脏和胰腺在稳态维持与适应性转变中的调控机制及相关疾病的分子基础。

代表性科研论文:


*corresponding author; #contribute equally


1. Ke-Ran Li#, Pei-Long Yu#, Qi-Qi Zheng#, Xin Wang, Xuan Fang, Lin-Chen Li and Cheng-Ran Xu*, Spatiotemporal and genetic cell lineage tracing of endodermal organogenesis at single-cell resolution. Cell, 188(3):796-813 (2025)

2. Li Yang#, Yu Zhang#, Xin-Xin Yu#, Yu-Heng Zhou#, Shuang He, Liu Yang, Tong-Yun Mao, Jun-Ge Yang, Ying Wu, Qi-Qi Zheng, Xun-Kai Li, Hou-Zao Chen, and Cheng-Ran Xu*, Hepatocyte metabolic adaptations during pregnancy and lactation. Cell, (online)

3. Liu Yang#, Xin-Xin Yu#, Xin Wang, Chen-Tao Jin and Cheng-Ran Xu*, The expression order determines the pioneer functions of Ngn3 and NeuroD1 in pancreatic endocrine differentiation. Science Advances, 28;11(13):eadt4770 (2025)

4. Yu Zhang#, Shuang He#, Xi Wang, Xin Wang, Mao-Yang He, Xin-Xin Yu and Cheng-Ran Xu*, ACSS2 mediates an epigenetic pathway to regulate β-cell adaptation during gestation. Nature Communications, 20;16(1):4697 (2025)

5. Xin-Xin Yu, Peng Peng, Chen-Tao Jin, Mao-Yang He, Shuang He, Liu Yang, Xi Wang, Jia-Xi Zheng, Jie Gao and Cheng-Ran Xu*, Comprehensive characterization of bihormonal cells and endocrine cell lineages in mammalian pancreatic islets. Advanced Science, doi: 10.1002/advs.202416326 (2025)

6. Li Yang#, Xin Wang#, Jia-Xi Zheng, Zi-Ran Xu, Lin-Chen Li, Yu-Long Xiong, Bi-Chen Zhou, Jie Gao and Cheng-Ran Xu*, Determination of key events in hepatocyte maturation at the single-cell level. Developmental Cell, 58(19):1996-2010 (2023)

7. Li Yang#, Xin Wang#, Xin-Xin Yu, Lu Yang, Jing Yang and Cheng-Ran Xu*, The default and directed pathways of bipotent hepatoblast differentiation involve distinct epigenomic mechanisms. Developmental Cell, 58(18): 1688-1700 (2023)

8. 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, 31(8): 886-903 (2021)

9. 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)

10. 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)

11. 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)

12. 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)

13. 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)

14. 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)

15. Li Yang, Lamaqiezhong and Cheng-Ran Xu*Molecular regulation mechanism of hepatic lineage differentiation and maturation. Chinese Journal of Cell Biology, 41(10):1853-1884 (2019)

16. 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)

17. 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)

18. 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)

19. 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)

20. 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)

21. 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)