Biography
Yinqing Li moved to Tsinghua in 2018, where he is now a tenured Associate Professor in the School of Pharmaceutical Sciences and a principal investigator at the IDG/McGovern Institute for Brain Research at Tsinghua. With training that spans microelectronics (B.S. Fudan University, 2008), systems engineering (S.M./Ph.D. Massachusetts Institute of Technology EECS, 2012/2016), and neuroscience (post-doctoral fellowship, the Broad Institute of Harvard and MIT and the Stanley Center for Psychiatric Research, 2016-2018), he leverages quantitative principles to drive cross-disciplinary advances in experimental genomics and neurobiology. Working with Feng Zhang, Aviv Regev and Guoping Feng, he co-invented single-nucleus multi-omics and helped engineer first-generation CRISPR tools for neuroscience. His lab now builds technologies that both read and rewrite gene regulation to tackle fundamental questions in ageing, degeneration, development and regeneration.
Yinqing has received fellowships and awards for his work, including MIT TR 35 under 35, China (2018), Extraordinary Potential Prize for Outstanding Self-financed Students Abroad, 10 Awardees Globally (2016), Wenner-Gren Fellowship (2016), and McGovern Institute Fellowship (2013).
People
Current Advisees and Students
Alumni
Current Research Interests
Cells encode their long-term “self” in chromatin marks that are, paradoxically, erased and rewritten reversibly. Our central question is therefore not “what marks exist?” but “how do reversible reactions maintain a stable equilibrium and what pushes the system over the ridge into disease?”
To dissect these processes, we combine wet-lab innovation with computational modelling, and we focus on two complementary systems: (1) Neuronal transcription and epigenetic homeostasis: How do neurons maintain activity-dependent gene programs for years? What breaks first in Alzheimer’s disease or addiction? (2) T-cell fate decisions: How does a T cell decide a balance between proliferating, killing, or exhaustion? Can we return the set-point to boost cancer therapy or curb autoimmunity?
We develop technologies to tackle these questions, including: single-cell temporal and spatial multi-omics, genome and epigenomic editing, and integrated computational analyses.
Scientific Contributions
- Transcriptional condensates in expression control and stability (Cell 2024)
- Attention network and cortical-thalamic circuity regulation (Nature 2020)
- Single nucleus omics for neuron and neural stem cell (Science 2016)
- Genome and epigenetic editing systems (Nature Biotechnology 2024)
- Systems biology and gene circuit
Publications
- Xu J, Jia Z, Zhao X, Wang L, Jin G, Li Z, Yin N, Li Y*, Peng M*. BCOR and ZC3H12A suppress a core stemness program in exhausted CD8+ T cells. JOURNAL OF EXPERIMENTAL MEDICINE. 2025 Aug 4;222(8):e20241133.
- Zhu M, Xu R, Yuan J, Wang J, Ren X, Cong T, You Y, Ju A, Xu L, Wang H, Zheng P, Tao H, Lin C, Yu H, Du J, Lin X, Xie W, Li Y*, Lan X*. Tracking-seq reveals the heterogeneity of off-target effects in CRISPR-Cas9-mediated genome editing. NATURE BIOTECHNOLOGY. 2024 Jul 2.
- He J, Huo X, Pei G, Jia Z, Yan Y, Yu J, Qu H, Xie Y, Yuan J, Zheng Y, Hu Y, Shi M, You K, Li T, Ma T, Zhang MQ, Ding S, Li P*, Li Y*. Dual-role transcription factors stabilize intermediate expression levels. CELL. 2024 Apr 10:S0092-8674(24)00314-3.
- Meng Q, Wei L, Ma K, Shi M, Lin X, Ho JWK, Li Y*, Zhang X*. scDecouple: decoupling cellular response from infected proportion bias in scCRISPR-seq. BRIEF BIOINFORM. 2024 Jan 22;25(2):bbae011.
- Lyu H, Yuan G, Liu X, Wang X, Geng S, Xia T, Zhou X, Li Y, Hu X, Shi Y. Sustained store-operated calcium entry utilizing activated chromatin state leads to instability in iTregs. ELIFE. 2023 Dec 6;12:RP88874.
- Zhu Z, Li D, Jia Z, Zhang W, Chen Y, Zhao R, Zhang YP, Zhang WH, Deng H, Li Y, Li W, Guang S, Ou G. Global histone H2B degradation regulates insulin/IGF signaling-mediated nutrient stress. THE EMBO JOURNAL. 2023 Oct 4;42(19):e113328.
- Xu Z, Ma D, Su H, Jia X, Li Y, Lu Y, Xie Z. Explore the dominant factor in prime editing via a view of DNA processing. SYNTHETIC AND SYSTEMS BIOTECHNOLOGY. 2023 Jun 3;8(3):371-377.
- Hu Y, Yang Y, Tan P, Zhang Y, Han M, Yu J, Zhang X, Jia Z, Wang D, Li Y, Ma T, Liu K, Ding S. Induction of mouse totipotent stem cells by a defined chemical cocktail. NATURE. 2022 Jun 21.
- Tan Y, Shen J, Si T, Ho CL, Li Y, Dai L. Engineered Live Biotherapeutics: Progress and Challenges. BIOTECHNOLOGY JOURNAL 2020 Oct;15(10):e2000155.
- Du J, Simmons S, Brunklaus A, Adiconis X, Hession CC, Fu Z, Li Y, Shema R, Møller RS, Barak B, Feng G, Meisler M, Sanders S, Lerche H, Campbell AJ, McCarroll S, Levin JZ, Lal D. Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders. EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY 2020 Jan;24:129-133.
- Li Y#, Lopez-Huerta VG#, Adiconis X#, Levandowski K, Choi S, Simmons SK, Arias-Garcia MA, Guo B, Yao AY, Blosser TR, Wimmer RD, Aida T, Atamian A, Naik T, Sun X, Bi D, Malhotra D, Hession CC, Shema R, Gomes M, Li T, Hwang E, Krol A, Kowalczyk M, Peça J, Pan G, Halassa MM, Levin JZ, Fu Z, Feng G. Distinct subnetworks of the thalamic reticular nucleus. NATURE. 2020 Jul;583(7818):819-824.
- Li Y, Weiss R., A Modular Approach to Building Complex Synthetic Circuits. Methods in Molecular Biology. 2017 pp. 231–248, DOI:10.1007/978-1-4939-7223-4_17.
- Yan WX, Mirzazadeh R, Garnerone S, Scott D, Schneider MW, Kallas T, Custodio J, Wernersson E, Li Y, Gao L, Federova Y, Zetsche B, Zhang F, Bienko M, Crosetto N., BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks. NATURE COMMUNICATIONS. 2017, 8:15058.
- Habib N#, Li Y#, Heidenreich M, Swiech L, Avraham-Davidi I, Trombetta JJ, Hession C, Zhang F, Regev A. Div-Seq: Single-nucleus RNA-Seq reveals dynamics of rare adult newborn neurons. SCIENCE. 2016, 353(6302):925-8.
- Yamano T, Nishimasu H, Zetsche B, Hirano H, Slaymaker IM, Li Y, Fedorova I, Nakane T, Makarova KS, Koonin EV, Ishitani R, Zhang F, Nureki O. Crystal Structure of Cpf1 in Complex with Guide RNA and Target DNA. CELL. 2016, 165(4):949-62.
- Nishimasu H, Cong L, Yan W, Ran F, Bernd Z, Li Y, Kurabayashi A, Ishitani R, Zhang F, Nureki O. Crystal structure of Staphylococcus aureus Cas9. CELL. 2015, 162(5):1113-26.
- Davidsohn N, Beal J, Kiani S, Adler A, Yaman F, Li Y, Xie Z, Weiss R. Accurate predictions of genetic circuit behavior from part characterization and modular composition. ACS SYNTHETIC BIOLOGY. 2015, 4(6):673-81.
- Li Y#, Jiang Y#, Chen H#, Liao W, Li Z, Weiss R, Xie Z. Modular construction of mammalian gene circuits using TALE transcriptional repressors. NATURE CHEMICAL BIOLOGY. 2015, 11(3):207-13.
- Swiech L, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Sur M, Zhang F. In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. NATURE BIOTECHNOLOGY. 2015, 33(1):102-6.
- Duportet X, Wroblewska L, Guye P, Li Y, Eyquem J, Rieders J, Rimchala T, Batt G, Weiss R. A platform for rapid prototyping of synthetic gene networks in mammalian cells. NUCLEIC ACIDS RESEARCH. 2014, 42(21):13440-51.
- Busskamp V, Lewis NE, Guye P, Ng AH, Shipman SL, Byrne SM, Sanjana NE, Murn J, Li Y, Li S, Stadler M, Weiss R, Church GM. Rapid neurogenesis through transcriptional activation in human stem cells. MOLECULAR SYSTEMS BIOLOGY. 2014, 10:760.
- Kiani S, Beal J, Ebrahimkhani MR, Huh J, Hall RN, Xie Z, Li Y, Weiss R. CRISPR transcriptional repression devices and layered circuits in mammalian cells. NATURE METHODS. 2014, 11(7):723-6.
- Hsu PD, Scott DA, Weinstein JA, Ran FA, Konermann S, Agarwala V, Li Y, Fine EJ, Wu X, Shalem O, Cradick TJ, Marraffini LA, Bao G, Zhang F. DNA targeting specificity of RNA-guided Cas9 nucleases. NATURE BIOTECHNOLOGY. 2013, 31(9):827-32.
- Guye P#, Li Y#, Wroblewska L, Duportet X, Weiss R. Rapid, modular and reliable construction of complex mammalian gene circuits. NUCLEIC ACIDS RESEARCH. 2013, 41(16):e156.
- Sakar MS, Neal D, Boudou T, Borochin MA, Li Y, Weiss R, Kamm RD, Chen CS, Asada HH. Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. LAB ON A CHIP. 2012, 12(23):4976-85.
- Zhao P, Li Y, Zeng X, Zhou J, Huang Y, Liu R. EWOD using P(VDF-TrFE). IEEE Nano/Micro Engineered and Molecular Systems. 2009, 10.1109/NEMS.2009.5068559.
- Zhao P, Li Y, Zhou J, Huang Y, Xie H, Xu H. A novel EWOD digital microuidic device using P(VDF-TrFE). IEEE Solid-State and Integrated-Circuit Technology. 2008, 10.1109/ICSICT.2008.4735080.
Courses