The liver and pancreas coordinately provide essential metabolic functions. During embryogenesis, both liver and pancreas progenitors derive from a common multipotent domain in the foregut endoderm and they share many aspects including several common transcriptional factors. Thereby the liver and pancreas development are usually considered together.
The goal of the laboratory is to investigate cell differentiation and organogenesis in liver and pancreas development, which is fundamental for the studies of liver and pancreas regeneration. Improved understanding of the programs of liver and pancreas development in embryogenesis could instruct us to sufficiently differentiate embryonic stem (ES) cells into specific liver or pancreas lineages for cell therapies of hepatic and pancreatic deceases.
Our studies are mainly focusing on the mechanisms of hepatocyte and β cell lineage specification and maturation during embryogenesis, which are precise process coordinated with extracellular cell signaling transduction, epigenetics, and genetic regulatory networks.
Representative Peer-Reviewed Publications
1. 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 (2019) e100164
2. 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, 2018
3.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, 2018
4. 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. JoVE, 2018
5. 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, 2018, 145(6):doi: 10.1242/dev.163162
6. Wei-Lin Qiu, Yu-Wei Zhang, Ye Feng, Lin-Chen Li, Liu Yang, Cheng-Ran Xu, Deciphering pancreatic islet β-cell and α-cell maturation pathways and characteristic features at the single-cell level. Cell Metabolism, 2017, 25:1194-1205
7. 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, 2017, 66(5):1387-1401
8. Ramkumar Mohan, Yi-Ping Mao, Shun-Gang Zhang, Yu-Wei Zhang, Cheng-Ran Xu, Gérard Gradwohl and Xiao-Qing Tang. Differentially expressed microRNA-483 confers distinct functions in pancreatic beta- and alpha-cells. Journal of Biological Chemistry, 2015, 32: 19955-19966
9. 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. EMBO J, 2014, 33: 2157-2170
10. Cheng-Ran Xu & Kenneth S. Zaret. Chromatin `Pre-Pattern` and Epigenetic Modulation in the Cell Fate Choice of Liver over Pancreas in the Endoderm. Nucleus, 3(2): 150-154 (2012)
11. 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)
12. 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)
13. 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)
14. 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）
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 (in press)