博士
北京大学未来技术学院 教授
北大-清华生命科学联合中心 研究员
国家杰出青年基金获得者
国家重点研发计划首席科学家
主要研究方向
揭示细胞谱系起源与命运的决定机制是发育生物学与医学研究的核心目标。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，发展新颖单细胞多维表观技术，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。本实验室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。利用我们发展的多种单细胞ChIP-seq技术(CoBATCH; itChIP; uCoTarget)、单细胞表观-转录双组学技术(CoTECH； uCoTargetX)与单细胞表观药物多组学技术（scEpiChem），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。实验室建立以来，在Nature Methods, Nature Cell Biology, Cell Stem Cell, Molecular Cell等重要学术期刊发表论文30余篇。
个人履历
2021-现在，北京大学未来技术学院分子医学研究所，教授
2014-2021，北京大学分子医学研究所，研究员
2014-现在，北大-清华生命科学联合中心，研究员
2012-2013，哈佛医学院波士顿儿童医院，讲师
2007-2012，哈佛医学院波士顿儿童医院，博士后
2004-2007，北京协和医学院基础医学院，理学博士
2003-2004，深圳国家生化工程中心，助理研究员
2000-2003，重庆医科大学基础医学院，硕士
1995-1999，湖北大学，学士
获奖及荣誉
2020，国家自然科学基金委，杰出青年基金
2020，勃林格殷格翰研究员奖
2018，拜尔学者奖
2016，北京大学绿叶生物医学奖
2014，中组部“海外高层次人才“
代表性论文(# ,共同通讯作者)
1. Dong C, Meng X, Zhang T, Guo Z, Liu Y, Wu P, Chen S, Zhou F, Ma Y, Shu S# and He A#. Single-cell EpiChem jointly measures drug-chromatin binding and multimodal epigenome. Nat Methods. In press. 2024
2. Xiong H, Wang Q, Li CC and He A. Single-cell joint profiling of multiple epigenetic proteins and gene transcription. Sci Adv. 2024;10:eadi3664.
3. Zhang Y, Li X, Gao S, Liao Y, Luo Y, Liu M, Bian Y, Xiong H, Yue Y#., He A#. Genetic reporter for live tracing fluid flow forces during cell fate regulation in mouse blastocyst development. Cell Stem Cell. 2023; 30(8):1110-1123.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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).
13. 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.
14. 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.
15. 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.
发表论文列表：
1. Dong C, Meng X, Zhang T, Guo Z, Liu Y, Wu P, Chen S, Zhou F, Ma Y, Shu S# and He A#. Single-cell EpiChem jointly measures drug-chromatin binding and multimodal epigenome. Nat Methods. In press. 2024
2. Xiong H, Wang Q, Li CC and He A. Single-cell joint profiling of multiple epigenetic proteins and gene transcription. Sci Adv. 2024;10:eadi3664.
3. Zhang Y, Li X, Gao S, Liao Y, Luo Y, Liu M, Bian Y, Xiong H, Yue Y#., He A#. Genetic reporter for live tracing fluid flow forces during cell fate regulation in mouse blastocyst development. Cell Stem Cell. 2023; 30(8):1110-1123.
4. Lei Z, Meng H, Liu L, Zhao H, Rao X, Yan Y, Wu H, Liu M, He A, Yi C. Mitochondrial base editor induces substantial nuclear off-target mutations. Nature, 2022; 606(7915):804-811
5. 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.
6. Li X, Liu D, Zhang L, Wang H, Li Y, Li Z, He A, Liu B, Zhou J, Tang F, Lan Y. The comprehensive DNA methylation landscape of hematopoietic stem cell development. Cell Discov. 2021,7(1):86.
7. 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.
8. 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.
9. Li R, Xia X, Wang X, Sun X, Dai Z, Huo D, Zheng H, Xiong H, He A, Wu X. Generation and validation of versatile inducible CRISPRi embryonic stem cell and mouse model. PLoS Biol. 2020, 18(11):e3000749
10. Xiong H and He A. Single-Cell Transcriptomic Analysis of Cardiac Progenitor Differentiation. Curr Cardiol Rep. 2020;22:38.
11. 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, in toto live imaging of cardiomyocyte behaviour during mouse ventricle chamber formation at single-cell resolution. Nat Cell Biol. 2020;22:332-340.
12. Hu X, Deng Q, Ma L, Li Q, Chen Y, Liao Y, Zhou F, Zhang C, Shao L, Feng J, He T, Ning W, Kong Y, Huo Y, He A, Liu B, Zhang J, Adams R, He Y, Tang F, Bian X and Luo J. Meningeal lymphatic vessels regulate brain tumor drainage and immunity. Cell Res. 2020;30:229-243.
13. Chang L, Li M, Shao S, Li C, Ai S, Xue B, Hou Y, Zhang Y, Li R, Fan X, He A, Li C and Sun Y. Nuclear peripheral chromatin-lamin B1 interaction is required for global integrity of chromatin architecture and dynamics in human cells. Protein Cell. 2020.
14. Ai S, Xiong H, Li CC, Luo Y, Shi Q, Liu Y, Yu X, Li C and He A. Profiling chromatin states using single-cell itChIP-seq. Nat Cell Biol. 2019;21:1164-1172.
15. 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.
16. Yang R, Cheng S, Luo N, Gao R, Yu K, Kang B, Wang L, Zhang Q, Fang Q, Zhang L, Li C, He A, Hu X, Peng J, Ren X and Zhang Z. Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis. Genome Biol. 2019;21:2.
17. Du Z, Zheng H, Kawamura YK, Zhang K, Gassler J, Powell S, Xu Q, Lin Z, Xu K, Zhou Q, Ozonov EA, Veron N, Huang B, Li L, Yu G, Liu L, Au Yeung WK, Wang P, Chang L, Wang Q, He A, Sun Y, Na J, Sun Q, Sasaki H, Tachibana K, Peters A and Xie W. Polycomb Group Proteins Regulate Chromatin Architecture in Mouse Oocytes and Early Embryos. Mol Cell. 2020;77:825-839 e7.
18. 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.
19. 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;125:198-208.
20. 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.
21. Liu L, Cai J, Wang H, Liang X, Zhou Q, Ding C, Zhu Y, Fu T, Guo Q, Xu Z, Xiao L, Liu J, Yin Y, Fang L, Xue B, Wang Y, Meng ZX, He A, Li JL, Liu Y, Chen XW and Gan Z. Coupling of COPII vesicle trafficking to nutrient availability by the IRE1alpha-XBP1s axis. Proc Natl Acad Sci U S A. 2019;116:11776-11785.
22. Ma C, Niu R, Huang T, Shao LW, Peng Y, Ding W, Wang Y, Jia G, He C, Li CY, He A and Liu Y. N6-methyldeoxyadenine is a transgenerational epigenetic signal for mitochondrial stress adaptation. Nat Cell Biol. 2019;21:319-327.
23. An NA, Ding W, Yang XZ, Peng J, He BZ, Shen QS, Lu F, He A, Zhang YE, Tan BC, Chen JY and Li CY. Evolutionarily significant A-to-I RNA editing events originated through G-to-A mutations in primates. Genome Biol. 2019;20:24.
24. 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.
25. Zhang M, Dong Y, Hu F, Yang D, Zhao Q, Lv C, Wang Y, Xia C, Weng Q, Liu X, Li C, Zhou P, Wang T, Guan Y, Guo R, Liu L, Geng Y, Wu H, Du J, Hu Z, Xu S, Chen J, He A, Liu B, Wang D, Yang YG and Wang J. Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes. Nat Immunol. 2018;19:279-290.
26. Han X, Luo S, Peng G, Lu J, Cui G, Liu L, Yan P, Yin Y, Liu Wei, Wang R, Zhang J, Ai S, Chang Z, Na J, He A, Jing N, Shen X. Mouse knockout models reveal largely dispensable but context-dependent functions of lncRNAs during development. Journal of Molecular Cell Biology, 2018;10(2):175-178.
27. Zhou P, Gu F, Zhang L, Akerberg BN, Ma Q, Li K, He A, Lin Z, Stevens SM, Zhou B and Pu WT. Mapping cell type-specific transcriptional enhancers using high affinity, lineage-specific Ep300 bioChIP-seq. Elife. 2017;6.
28. Zhang S-J, Wang C, Yan S, Fu A, Luan X, Li Y, Sunny Shen Q, Zhong X, Chen J-Y, Wang X, Chin-Ming Tan B, He A and Li C-Y. Isoform Evolution in Primates through Independent Combination of Alternative RNA Processing Events. Mol Biol Evol. 2017;34:2453-2468.
29. Yang Y, Liu B, Xu J, Wang J, Wu J, Shi C, Xu Y, Dong J, Wang C, Lai W, Zhu J, Xiong L, Zhu D, Li X, Yang W, Yamauchi T, Sugawara A, Li Z, Sun F, Li X, Li C, He A, Du Y, Wang T, Zhao C, Li H, Chi X, Zhang H, Liu Y, Li C, Duo S, Yin M, Shen H, Belmonte JCI and Deng H. Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency. Cell. 2017;169:243-257.e25.
30. Wang F, Song W, Zhao H, Ma Y, Li Y, Zhai D, Pi J, Si Y, Xu J, Dong L, Su R, Zhang M, Zhu Y, Ren X, Miao F, Liu W, Li F, Zhang J, He A, Shan G, Hui J, Wang L and Yu J. The RNA-binding protein QKI5 regulates primary miR-124-1 processing via a distal RNA motif during erythropoiesis. Cell Res. 2017;27:416-439.
31. Han X, Li P, Yang Z, Huang X, Wei G, Sun Y, Kang X, Hu X, Deng Q, Chen L, He A, Huo Y, Li D, Betzig E and Luo J. Zyxin regulates endothelial von Willebrand factor secretion by reorganizing actin filaments around exocytic granules. Nat Commun. 2017;8:14639.
32. 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.
33. 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.
34. Xiao C, Gao L, Hou Y, Xu C, Chang N, Wang F, Hu K, He A, Luo Y, Wang J, Peng J, Tang F, Zhu X and Xiong J-W. Chromatin-remodelling factor Brg1 regulates myocardial proliferation and regeneration in zebrafish. Nat Commun. 2016;7:13787.
35. Lin Z, Guo H, Cao Y, Zohrabian S, Zhou P, Ma Q, VanDusen N, Guo Y, Zhang J, Stevens SM, Liang F, Quan Q, van Gorp PR, Li A, Dos Remedios C, He A, Bezzerides VJ and Pu WT. Acetylation of VGLL4 Regulates Hippo-YAP Signaling and Postnatal Cardiac Growth. Dev Cell. 2016.
36. Prendiville TW, Guo H, Lin Z, Zhou P, Stevens SM, He A, VanDusen N, Chen J, Zhong L, Wang D-Z, Gao G and Pu WT. Novel Roles of GATA4/6 in the Postnatal Heart Identified through Temporally Controlled, Cardiomyocyte-Specific Gene Inactivation by Adeno-Associated Virus Delivery of Cre Recombinase. PLoS One. 2015;10:e0128105.
37. Chen J-Y, Shen QS, Zhou W-Z, Peng J, He BZ, Li Y, Liu C-J, Luan X, Ding W, Li S, Chen C, Tan BC-M, Zhang YE, He A and Li C-Y. Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates. PLoS Genet. 2015;11:e1005391.
38. Wang G, McCain ML, Yang L, He A, Pasqualini FS, Agarwal A, Yuan H, Jiang D, Zhang D, Zangi L, Geva J, Roberts AE, Ma Q, Ding J, Chen J, Wang D-Z, Li K, Wang J, Wanders RJA, Kulik W, Vaz FM, Laflamme MA, Murry CE, Chien KR, Kelley RI, Church GM, Parker KK and Pu WT. Modeling the mitochondrial cardiomyopathy of Barth syndrome with induced pluripotent stem cell and heart-on-chip technologies. Nat Med. 2014;20:616-23.
39. Wang F, Zhu Y, Guo L, Dong L, Liu H, Yin H, Zhang Z, Li Y, Liu C, Ma Y, Song W, He A, Wang Q, Wang L, Zhang J, Li J and Yu J. A regulatory circuit comprising GATA1/2 switch and microRNA-27a/24 promotes erythropoiesis. Nucleic Acids Res. 2014;42:442-57.
40. Prendiville TW, Ma Q, Lin Z, Zhou P, He A and Pu WT. Ultrasound-guided Transthoracic Intramyocardial Injection in Mice. J Vis Exp. 2014.
41. He A, Gu F, Hu Y, Ma Q, Yi Ye L, Akiyama JA, Visel A, Pennacchio LA and Pu WT. Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease. Nat Commun. 2014;5:4907.
42. Aronson BE, Rabello Aronson S, Berkhout RP, Chavoushi SF, He A, Pu WT, Verzi MP and Krasinski SD. GATA4 represses an ileal program of gene expression in the proximal small intestine by inhibiting the acetylation of histone H3, lysine 27. Biochim Biophys Acta. 2014.
43. Zhou P, Zhang Y, Ma Q, Gu F, Day DS, He A, Zhou B, Li J, Stevens SM, Romo D and Pu WT. Interrogating translational efficiency and lineage-specific transcriptomes using ribosome affinity purification. Proc Natl Acad Sci U S A. 2013;110:15395-400.
44. Ge F, Yuan S, Su L, Shen Z, He A, Huang T and Gong W. Alteration of innate immunity by donor IL-6 deficiency in a presensitized heart transplant model. PLoS One. 2013;8:e77559.
45. Zhou P, He A and Pu WT. Regulation of GATA4 Transcriptional Activity in Cardiovascular Development and Disease. Curr Top Dev Biol. 2012;100:143-69.
46. Ounzain S, Kobayashi S, Peterson RE, He A, Motterle A, Samani NJ, Menick DR, Pu WT, Liang Q and Chong NW. Cardiac expression of ms1/STARS, a novel gene involved in cardiac development and disease, is regulated by GATA4. Mol Cell Biol. 2012;32:1830-43.
47. He A, Shen X, Ma Q, Cao J, von Gise A, Zhou P, Wang G, Marquez VE, Orkin SH and Pu WT. PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev. 2012;26:37-42.
48. He A and Pu WT. Mature Cardiomyocytes Recall Their Progenitor Experience Via Polycomb Repressive Complex 2. Circulation Research. 2012;111:162-164.
49. He A, Ma Q, Cao J, von Gise A, Zhou P, Xie H, Zhang B, Hsing M, Christodoulou DC, Cahan P, Daley GQ, Kong SW, Orkin SH, Seidman CE, Seidman JG and Pu WT. Polycomb Repressive Complex 2 Regulates Normal Development of the Mouse Heart. Circ Res. 2012;110:406-15.
50. Seok HY, Tatsuguchi M, Callis TE, He A, Pu WT and Wang DZ. miR-155 inhibits expression of the MEF2A protein to repress skeletal muscle differentiation. J Biol Chem. 2011;286:35339-46.
51. Kuttippurathu L, Hsing M, Liu Y, Schmidt B, Maskell DL, Lee K, He A, Pu WT and Kong SW. CompleteMOTIFs: DNA motif discovery platform for transcription factor binding experiments. Bioinformatics. 2011;27:715-7.
52. He A, Kong SW, Ma Q and Pu WT. Co-occupancy by multiple cardiac transcription factors identifies transcriptional enhancers active in heart. Proc Natl Acad Sci U S A. 2011;108:5632-7.
53. He A and Pu WT. Genome-wide location analysis by pull down of in vivo biotinylated transcription factors. Curr Protoc Mol Biol. 2010;Chapter 21:Unit 21.20.
54. Ikeda S, He A, Kong SW, Lu J, Bejar R, Bodyak N, Lee KH, Ma Q, Kang PM, Golub TR and Pu WT. MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes. Mol Cell Biol. 2009;29:2193-204.
55. He A, Zhu L, Gupta N, Chang Y and Fang F. Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol. 2007;21:2785-94.
56. He A, Liu X, Liu L, Chang Y and Fang F. How many signals impinge on GLUT4 activation by insulin? Cell Signal. 2007;19:1-7.
57. Yang C, Yang Y, Gupta N, Liu X, He A, Liu L, Zuo J, Chang Y, Fang F. Pentaspan membrane glycoprotein, prominin-1, is involved in glucose metabolism and cytoskeleton alteration. Biochemistry (Mosc). 2007;72(8):854-62.
58. Liu L, He A, Liu X, Li Y, Chang Y, Fang F. Protein kinase Czeta and glucose uptake. Biochemistry (Mosc). 2006;71(7):701-6.
59. Liu X, He A, Chang Y, Fang F. Atypical protein kinase C in glucose metabolism. Cell Signal. 2006;18(12):2071-6.