研究方向:
解码细胞命运的决定机制是发育、再生及疾病过程中的核心问题。本实验室主要围绕细胞命运决定的表观遗传调控机制及器官尺度细胞谱系规律,发展新颖单细胞表观多组学测序技术,整合光学成像、图像处理和机器学习等多学科交叉的手段,研究器官发生、再生和疾病发生的分子细胞学机理。我们同时围绕疾病的早期诊断和人类癌症的临床治疗面临的耐药与复发的细胞命运调控开展深入研究。利用我们开发的多种单细胞ChIP-seq技术(CoBATCH; itChIP)与单细胞表观-转录双组学技术(CoTECH),以及哺乳动物胚胎显微操作技术和基因编辑技术,以单细胞分辨率或单分子水平深入研究细胞命运改变的多模态分子调控机制,提供高灵敏度早期疾病无创诊断和疾病治疗策略。本实验室还致力于整合实时成像图像分析与单细胞多组学测序数据,跟踪细胞命运,以期可以记录和还原活体胚胎或组织器官发育整个过程的全局分子调控和细胞谱系图。近5年以通讯作者在Nature Methods, Nature Cell Biology (2篇), Molecular Cell, Circulation Research(3篇), 和PNAS等发表多篇学术论文。
代表性科研论文:
1. Li C C, Zhang G, Du J, Li Z, Ni Y, Zhou J, Li Y, Hou S, Zheng X, Lan Y#, Liu B#, He A#. Pre-configuring chromatin architecture with histone modifications guides hematopoietic stem cell formation in mouse embryos. Nat Commun., 2022; 13(1): 1-13.
2. Li X, Yue Y, Zhang Y, Liao Y, Wang Q, Bian Y, Na J, He A. Continuous live imaging reveals a subtle pathological alteration with cell behaviors in congenital heart malformation. Fundamental Research, 2022, 2(1): 14-22.
3. Xiong H, Luo Y, Wang Q, Yu X and He, A. Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions. Nat Methods. 2021; 18(6):652-660.
4. Yue Y, Zong W, Li X, Li J, Zhang Y, Wu R, Liu Y, Cui J, Wang Q, Bian Y, Yu X, Liu Y, Tan G, Zhang Y, Zhao G, Zhou B, Chen L, Xiao W#, Cheng H#, and He, A#. Long-term live imaging reconstructs in toto cardiomyocyte behaviors underlying mammalian heart chamber formation. Nat Cell Biol. 2020; 22, 332–340.
5. Ai S, Xiong H, Li CC, Luo Y, Shi Q, Liu Y, Yu X, Li C and He A. Profiling chromatin state by single-cell itChIP-seq. Nat Cell Biol. 2019; 21(9):1164-1172.
6. Wang Q, Xiong H, Ai S, Yu X, Liu Y, Zhang J and He A. CoBATCH for High-throughput Single-cell Epigenomic Profiling. Mol Cell. 2019; 76(1):206-216.
7. Xiong H, Luo Y, Yue Y, Zhang J, Ai S, Li X, Wang X, Zhang YL, Wei Y, Li H, Hu X, Li C and He A. Single-Cell Transcriptomics Reveals Chemotaxis Mediated Intra-Organ Crosstalk During Cardiogenesis. Circ Res. 2019; 125(4):398-410.
8. Li Y, Ai S, Yu X, Li C, Li X, Yue Y, Wei Y, Li CY# and He A#. Replication-Independent Histone Turnover Underlines the Epigenetic Homeostasis in Adult Heart. Circ Res. 2019; 125(2):198-208.
9. Han X, Zhang J, Liu Y, Fan X, Ai S, Luo Y, Li X, Jin H, Luo S, Zheng H, Yue Y, Chang Z, Yang Z, Tang F, He A# and Shen X#. The lncRNA Hand2os1/Uph locus orchestrates heart development through regulation of precise expression of Hand2. Development. 2019; 146(13).
10. Li Y, Li C, Li S, Peng Q, An NA, He A# and Li CY#. Human exonization through differential nucleosome occupancy. Proc Natl Acad Sci U S A. 2018;115:8817-8822.
11. Ai S, Yu X, Li Y, Peng Y, Li C, Yue Y, Tao G, Li C-Y, Pu WT and He A. Divergent Requirements for EZH1 in Heart Development Versus Regeneration. Circ Res. 2017;121:106-112.
12. Ai S, Peng Y, Li C, Gu F, Yu X, Yue Y, Ma Q, Chen J, Lin Z, Zhou P, Xie H, Prendiville TW, Zheng W, Liu Y, Orkin SH, Wang D-Z, Yu J, Pu WT# and He A#. EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. Elife. 2017;6.