Aiben He, Ph.D.
Epigenomics and Cell Fate Engineering
Professor, College of Future Technology, Peking University
tel：
E-mail：ahe@pku.edu.cn
1. Deciphering regulation of cell fate decisions during development and human diseases (single cell multi-omics, bioinformatics, and mouse and human genetics)
2. Developing novel cell fate engineering, single-cell multi-omics and cell-free epigenomics technologies for cellular therapy and diagnosis
3. Tracing cellular origins of embryonic development (long-term live imaging and digital lineages)
1. Single-cell omics technologies for probing complex gene regulation and cell fate.
CoTECH is a joint method for profiling transcriptome and chromatin occupancy simultaneously in single-cells. We integrated our previously developed CoBATCH (Wang et al., Molecular Cell, 2019) together with modified single-cell RNA-seq method, to simultaneously profile gene expression and chromatin binding in the same single cells. Furthermore, by aggregating data from cells with similar transcriptome (data from different experimental batches), we can obtain “pseudosingle-cells” that contain information of several histone modifications or TFs binding, enabling higher-dimensional epigenomic reconstruction. (Xiong et al., Nature Methods, 2021)
To investigate the heterogeneity of cellular responses to small-molecule drugs in tumors, our team developed scEpiChem (Dong et al., Nature Methods, 2024), a groundbreaking technology that captures genome-wide binding sites of small-molecule drugs at single-cell resolution while simultaneously profiling both drug-target interactions and multi-omic epigenetic states. This single-cell approach for drug-target mapping and its derived innovations hold transformative potential for advancing clinical drug efficacy evaluation, deciphering tumor resistance mechanisms, and accelerating the development of novel therapies and precision drugs.
We developed high throughput single-cell multi-epigenomics method, dubbed uCoTarget(X), for single-cell joint profiling of up to six histone modifications and/or transcriptome (Xiong et al., Sci Adv, 2024). Excitingly, we next developed revolutionary methods for genome-coverage single-cell histone modification profiling with extraordinarily high precision, TACIT and CoTACIT (Liu et al., Nature, 2025). For the first time, our work revealed how epigenetic heterogeneity is initiated as early as the two-cell stage and identified key transcription factors and transposable elements governing the exit from totipotency and the first cell fate determination. These findings provide unprecedented insights into the epigenetic regulation of early embryonic development, offering a transformative framework for understanding cell lineage specification and developmental plasticity.
2. In toto live imaging for lineage reconstructions of organogenesis and regeneration.
A central theme in organogenesis is how cell lineages of pergent sources are spatiotemporally deployed to assemble complex organ structures in mammals. Our team overcame the technical challenges by optimizing mouse embryo culture and mounting methods, developing a vertical, dual-side illumination light-sheet microscope (vLSFM), equipping it with an integrated embryo culture module, together with a heartbeat-gated imaging module. With this integrative approach, we realized a 36-h, all cell-resolved imaging of developing mouse heart at 3-min intervals. Concepts derived include a new perspective for how dynamic cell behaviors are coordinated in the pivotal events of heart morphogenesis – ventricular chamber ballooning and trabeculation, challenging while unifying prevalent views based on classic population or single-cell snapshot analyses. Our work also paves the way for continuous live imaging of multi-scaled grand developmental schemes of organogenesis as well as subtle pathological alterations, e.g., in congenital heart disease models.
3. cf-EpiTracing of plasma chromatin states infers disease cell types of origin and therapeutic response
Chromatin carries epigenetic signatures indicative of tissue origin, cellular identity, and disease progression. Our team has pioneered cf-EpiTracing, a non-invasive epigenetic diagnostic technology that efficiently detects and integrates multimodal epigenomic information from plasma cell-free chromatin. This innovation establishes an unbiased multi-organ monitoring platform, enabling comprehensive applications in early cancer screening across multiple tumor types, myocardial infarction risk prediction, dynamic tracking of disease progression and aging, and evaluation of treatment efficacy and prognosis. By decoding the epigenetic landscape of circulating chromatin, cf-EpiTracing offers a transformative tool for precision medicine and proactive health management.
Dong C, Meng X, Zhang T, Guo Z, Liu Y, Wu P, Chen S, Zhou F, Ma Y, Xiong H, Shu S and He AB. (2024) Single-cell EpiChem jointly measures drug-chromatin binding and multimodal epigenome. Nat. Methods, 21: 1624-1633.
Xiong H, Wang Q, Li C C, He AB. (2024) Single-cell joint profiling of multiple epigenetic proteins and gene transcription. Sci. Adv., 10: eadi3664.
Xiong H, Wang R, He AB. (2023) Single-cell protein-DNA interactomics and multiomics tools for deciphering genome regulation. National Science Open, 2: 20220057.
Zhang Y, Li X, Gao S, Liao Y, Luo Y, Liu M, Bian Y, Xiong H, Yue Y, He AB. (2023) Genetic reporter for live tracing fluid flow forces during cell fate segregation in mouse blastocyst development. Cell Stem Cell, 30: 1110-1123.
Li C, Wu B, Li Y, Liu Y, Wang J, Xie J, Xu X, Tian X, Ye Z, Guan J, Chen J, Xie S, Zhang B, Cai B, Wang Q, Yu H, Lan T, Man C, Kang X, Qian P, Perry J, He AB, Jiang L, Zhao M. (2022) Loss of sphingosine kinase 2 promotes the expansion of hematopoietic stem cells by improving their metabolic fitness. Blood, 140: 1686-1701.
Lei Z, Meng H, Liu L, Zhao H, Rao X, Yan Y, Wu H, Liu M, He A, Yi C. (2022) Mitochondrial base editor induces substantial nuclear off-target mutations. Nature, 606: 804-811.
Li C C, Zhang G, Du J, Li Z, Ni Y, Zhou J, Li Y, Hou S, Zheng X, Lan Y, Liu B, He AB. (2022) Pre-configuring chromatin architecture with histone modifications guides hematopoietic stem cell formation in mouse embryos. Nat. Commun., 13: 346.
Li X, Yue Y, Zhang Y, Liao Y, Wang Q, Bian Y, Na J, He AB. (2022) Continuous live imaging reveals a subtle pathological alteration with cell behaviors in congenital heart malformation. Fundam. Res., 2: 14-22.
Xiong H, Luo Y, Wang Q, Yu X, He AB. (2021) Single-cell joint detection of chromatin occupancy and transcriptome enables higher-dimensional epigenomic reconstructions. Nat. Methods, 18: 652-660.
Xiong H, He AB. (2020) Single-Cell Transcriptomic Analysis of Cardiac Progenitor Differentiation. Curr. Cardiol. Rep., 22: 38.
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 AB. (2020) Long-term, in toto live imaging of cardiomyocyte behaviour during mouse ventricle chamber formation at single-cell resolution. Nat. Cell Biol., 22: 332-340.
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 AB, Liu B, Zhang J, Adams R, He Y, Tang F, Bian X, Luo J. (2020) Meningeal lymphatic vessels regulate brain tumor drainage and immunity. Cell Res., 30: 229-243.
Chen Li, Jie Li, Min Liu, Shuaifang Yan, Xiaoxuan Meng, Xubin Chen, Kexin Xian, Tong Zhang, Liuxian Zheng, Runxuan Zhao
