研究方向:
哺乳动物基因组中98%的部分是非编码DNA,这些非编码DNA不仅是染色体三维结构的主要组成部分,而且含有大量的基因转录调控元件,如增强子和抑制子。染色体三维结构和非编码调控元件的动态变化,调控着基因的多样性表达,进而产生生命体中各种细胞类型。因此,发现并诠释这些非编码调控元件的基因调控功能是我们理解细胞多样性和表型复杂性的关键切入点。本实验室利用单细胞多组学和基因组编辑等多种研究技术,研究细胞分化,器官形成,以及疾病发生等生物模型中的染色体构象和非编码调控元件的动态变化和功能。基于调控元件与其靶基因在三维空间形成染色体环,我们将首先利用单细胞染色体构象捕获等技术研究转录调控元件与其靶向基因在不同细胞状态下的对应关系,构建基因与调控元件的连接网络。我们还将结合高通量的基因编辑技术在不同生物学状态下对非编码调控元件的功能进行测定,从而帮助我们理解和阐释非编码调控元件的基因调控分子机理。围绕这些问题,我们也将积极开发单细胞表观遗传组学和三维组学新技术,并探索新技术和非编码调控元件在人类发育、疾病、衰老等方向的应用。
代表性科研论文:
1. Guoqiang Li*, Yaping Liu*, Yanxiao Zhang, Naoki Kubo, Miao Yu, Rongxin Fang, Manolis Kellis and Bing Ren. “Joint profiling of DNA methylation and chromatin architecture in single cells.” Nature Methods, 16 (2019): 991–993.
2. Xiaocui Xu*, Guoqiang Li*, Congru Li*, Jing Zhang*, Qiang Wang*, David K Simmons, Xuepeng Chen, Naveen Wijesena, Wei Zhu, Zhanyang Wang, Zhenhua Wang, Bao Ju, Weimin Ci, Xuemei Lu, Daqi YuQian-fei Wang, Neelakanteswar Aluru, Paola Oliveri, Yong E Zhang, Mark Q Martindale and Jiang Liu. “Evolutionary transition between invertebrates and vertebrates via methylation reprogramming in embryogenesis.” National Science Review, nwz064 (2019)
3. Congru Li*, Yang Yu*, Yong Fan*, Guoqiang Li*, Xiaocui Xu, Jialei Duan, Rong Li, Xiangjin Kang, Xin Ma, Xuepeng Chen, Yuwen Ke, Jie Yan, Ying Lian, Ping Liu, Yue Zhao, Hongcui Zhao, Yaoyong Chen, Xiaofang Sun, Jianqiao Liu, Jie Qiao and Jiang Liu. “DNA methylation reprogramming of functional elements during mammalian embryonic development.” Cell Discovery 4, no. 28 (2018).
4. Guoqiang Li*, Yang Yu*, Yong Fan*, Congru Li*, Xiaocui Xu, Jialei Duan, Rong Li, Xiangjin Kang, Xin Ma, Xuepeng Chen, Yuwen Ke, Jie Yan, Ying Lian, Ping Liu, Yue Zhao, Hongcui Zhao, Yaoyong Chen, Xiaofang Sun, Jianqiao Liu, Jie Qiao and Jiang Liu. “Genome-wide abnormal DNA methylome of human blastocyst in assisted reproductive technology.” Journal of Genetics and Genomics 44 (2017): 475-481.
5. Guoqiang Li*, Weimin Ci*, Subhradip Karmakar*, Ke Chen, Zhixiang Fan, Zhongqiang Guo, Jing Zhang, Lu Wang, Min Zhuang, Shengdi Hu, Xuesong Li, Xianghong Li, Matthew F. Calabrese, Edmond R. Watson, Sandip Prasad, Carrie Rinker-Schaeffer, Scott E. Eggener, Thomas Stricker, Yong Tian, Brenda Schulman, Jiang Liu and Kevin P. White. “SPOP promotes tumorigenesis by acting as a key regulatory hub in kidney cancer.” Cancer Cell 25, no. 4 (2014): 455-468.