Research Area:

The He lab has a long-standing interest in principles in controlling cell fate decisions and coordinating cell behaviors for mammalian organ formation, and cardiovascular diseases and regeneration To achieve these goals, we have developed a number of novel technologies, including single-cell ChIP-seq (itChIP and CoBATCH) and in toto live-imaging in recent years. We, for the first time, presented a framework of coupling long-term live imaging with digital lineage reconstructions to track uninterrupted cell lineage histories across their past, present, and future to reveal organ-level morphogenetic mechanisms in mammals. Further efforts are directed to devise new single-cell multimodal omics to elucidate the epigenetic mechanisms of gene regulation during cell fate determination, and integrate time-resolved live-imaging methods with single-cell molecular profiling to decipher the holistic blueprint for organ generation and regeneration. We also aspire to apply these cool technologies to early diagnosis of diseases, including myocardial infarction and various blood diseases. We are an interdisciplinary team, combining expertise from developmental biology, epigenetics, bioinformatics, light-sheet microscopy, quantitative imaging analysis and mathematical modeling.

Lab members:

PI：Aibin He  Ph.D  Email: ahe@pku.edu.cn

Students:  Shanshan Ai, Yingjie Luo, Xin Li, Yanzhu Yue, Xianhong Yu, Haiqing Xiong, Chen Li, Jiejie Zhang, Youdong Zhang, Qianhao Zhang, Yaqian Liu, Yunkun Bian

Undergraduate: Min Liu (Sichuan University), Xin Li (Peking University), Yuanhui Liao (Beijing University of Technology)

Lab address: Integrated Science Research Building, Room 220-221, Peking University, Beijing 100871.Telephone

Telephone number: 010-6274-4560

Main research articles:

1. 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. Nature Cell Biology. 2020; 22, 332–340.

2. 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. Nature Cell Biology. 2019; 21(9):1164-1172.

3. 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.

4. 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.

5. 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.

6. 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).

7. 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.

8. 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.

9. 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.

10. Chen JY, Shen QS, Zhou WZ, Peng J, He BZ, Li Y, Liu CJ, Luan X, Ding W, Li S, Chen C, Tan BC, Zhang YE, He A^#, Li CY^#. Emergence, Retention and Selection: A Trilogy of Origination for Functional De Novo Proteins from Ancestral LncRNAs in Primates. PLoS Genet. 2015;11:e1005391.

11. He A^#*, Gu F^*, Hu Y, Ma Q, Yi Ye L, Akiyama JA, Visel A, Pennacchio LA, Pu WT^#. Dynamic GATA4 enhancers shape the chromatin landscape central to heart development and disease. Nat Commun. 2014;5:4907.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

Collaborative publications:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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.

18. Prendiville TW, Ma Q, Lin Z, Zhou P, He A and Pu WT. Ultrasound-guided Transthoracic Intramyocardial Injection in Mice. J Vis Exp. 2014.

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. 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.

Reviews or Book chapters:

1. Xiong H and He A. Single-cell Transcriptomic analysis of cardiac progenitor differentiation. Current Cardiology Reports. In press.

2. He A and Pu WT. Mature Cardiomyocytes Recall Their Progenitor Experience Via Polycomb Repressive Complex 2. Circulation Research. 2012;111:162-164.

3. 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.

4. 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.

Patents:

1. Abin He, Shanshan Ai, and Chen Li. Micro-ChIP (itChIP) Method. PCT patent number: WO/2019/153852.

2. Abin He, Shanshan Ai, and Yingjie Luo. A Fusion protein for ChIP-seq kit (CoBATCH). PCT patent number: WO/2019/153851.

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