基本信息
李令杰
干细胞分化发育与疾病的表观遗传调控研究组
电话：63846590-776901
邮箱：lingjie@shsmu.edu.cn
研究方向
本实验室的主要研究兴趣为细胞命运的决定机制，目前专注于皮肤分化发育的表观基因组调控以及再生医学研究。实验室以上皮系统特别是皮肤器官为主要研究对象，运用多种表观基因组分析技术，并结合体外干细胞分化与体内发育模型来深入理解：早期外胚层及上皮组织谱系特化、稳态平衡、衰老及相关疾病发生的调控机制；在此基础上进一步发展干细胞及基因组新技术/方法用于再生医学及复杂疾病的诊治。
过往的研究成绩包括：发现干细胞命运关键蛋白Stk40，并揭示该蛋白调控核内转录因子与外界信号通路之间的应答机制（PNAS 2010）;构建动物模型并揭示出长链非编码RNA调控胚胎发育、肿瘤和基因组中染色质失活的重要功能（Cell Rep.2013, Elfie 2022）;合作开发出人皮肤干细胞分化系统用于治疗遗传性皮肤缺损症以及类器官模型用于皮肤再生与药物筛选，并系统揭示出外胚层及皮肤发育各阶段的表观基因组调控规律(Cell Stem Cell 2019)；建立单细胞发育潜能以及染色质互作的生信分析工具，促进对细胞命运调控机理的研究(Brief Bioinform 2022, 2023)。
个人简历
目前担任上海交通大学基础医学院组织胚胎学与遗传发育学系课题组长，博士生导师。西北大学生物技术专业学士，中科院上海生命科学研究院发育生物学博士，美国斯坦福大学博士后及Research Associate。主要研究成果发表在Cell Stem Cell，Cell Rep，PNAS，Brief Bioinform, Elfie等国际知名期刊。
科研项目
1. 细胞周期和DNA甲基化在多能性建立、维持和退出过程中的功能和机制研究，科技部重点研发计划，2021-2026，项目子课题负责人；
2. 皮肤分化早期细胞群体的异质性及功能与调节机制的研究，国家自然科学基金委面上项目，2021-2024，课题负责人；
3. TFAP2C调控体表外胚层干细胞分化潜能的表观遗传学机制，上海市科委项目，2021-2024，课题负责人
4. 上海高层次人才计划，上海市教委，2019-2021，课题负责人
5. 上海交通大学医学院新课题组启动经费,课题负责人。
论文与专著
1) Zhang F, Jiao H, Wang Y, Yang C, Li L, Wang Z, Tong R, Zhou J, Shen J,Li L. InferLoop: leveraging single-cell chromatin accessibility for the signal of chromatin loop.Brief Bioinform. 2023 May 19;24(3):bbad166. doi: 10.1093/bib/bbad166.
2) Lan L, Zhang X, Yang S,Li L, Mao X. Chromosome-level genome assembly of the Stoliczka's Asian trident bat (Aselliscus stoliczkanus). Sci Data. 2023;10(1):902. Published 2023 Dec 15. doi:10.1038/s41597-023-02838-0
3) Ma Q, Yang L, Tolentino K, Wang G, Zhao Y, Litzenburger UM, Shi Q, Zhu L, Yang C, Jiao H, Zhang F, Li R, Tsai MC, Chen JA, Lai I, Zeng H,Li L, Chang HY. Inducible lncRNA transgenic mice reveal continual role of HOTAIR in promoting breast cancer metastasis.Elife.2022 Dec 29;11:e79126. doi: 10.7554/eLife.79126.
4) Zhang F, Yang C, Wang Y, Jiao H, Wang Z, Shen J,Li L. FitDevo: accurate inference of single-cell developmental potential using sample-specific gene weight.Brief Bioinform. 2022 Sep 20;23(5):bbac293. doi: 10.1093/bib/bbac293.
5) Li L, Wang Y, Torkelson JL, Shankar G, Pattison J, H Zhen, Duren Z, Fang F, Melo S, Piekos S, Li J, Liaw E, Chen L, Li R, Wernig M, Wong WH, Chang HY, Oro AE. TFAP2C- and p63-Dependent Networks Sequentially Rearrange Chromatin Landscapes to Drive Human Epidermal Lineage Commitment.Cell Stem Cell2019 24:271-284
6) Li L, Helms JA, Chang HY. Comment on "Hotair Is Dispensable for Mouse Development".PLoS Genetics. 2016 Dec 15;12(12):e1006406. doi: 10.1371/journal.pgen.1006406. eCollection 2016.
7) Li L, Chang HY. PhysiologicalrolesoflongnoncodingRNAs:insightfromknockout mice.Trends in Cell Biology.2014 24(10): 594-602.
8) Li L,Liu B, Wapinski OL, Tsai MC, Qu K, Zhang J, Carlson JC, Lin M, Fang F, Gupta RA, Helms JA, Chang HY. Targeted disruption of Hotair leads to homeotic transformation and gene derepression. CellReports. 2013 5(1): 3-12.
9) Li L, Sun L, Gao F, Jiang J, Yang Y, Li C, Gu J, Wei Z, Yang A, Lu R, Ma Y, Tang F, Won Kwon S, Zhao Y, Li J, Jin Y. Stk40 links the pluripotency factor Oct4 to the Erk/MAPK pathway and controls extraembryonic endoderm differentiation.PNAS.2010 107(4): 1402-7.
10)Yao, T., Zhang, Z., Li, Q., Huang, R., Hong, Y., Li, C., Zhang, F., Huang, Y., Fang, Y., Cao, Q., Jin, X., Li, C., Wang, Z., Lin, X. J.,Li, L., Wei, W., Wang, Z., & Shen, J. Long-Read Sequencing Reveals Alternative Splicing-Driven, Shared Immunogenic Neoepitopes Regardless of SF3B1 Status in Uveal Melanoma. Cancer Immunol Res, 2023,11(12), 1671–1687.
11)Fang F, Cao W, Mu Y, Okuyama H,Li L, Qiu J, Weyand CM, Goronzy JJ. IL-4 prevents adenosine-mediated immunoregulation by inhibiting CD39 expression.JCI Insight. 2022 Jun 22;7(12):e157509. doi: 10.1172/jci.insight.157509.
12)Yang W, He H, Wang T, Su N, Zhang F, Jiang K, Zhu J, Zhang C, Niu K, Wang L, Yuan X, Liu N,Li L, Wei W, Hu J. Single-Cell Transcriptomic Analysis Reveals a Hepatic Stellate Cell-Activation Roadmap and Myofibroblast Origin During Liver Fibrosis in Mice.Hepatology. 2021 Nov;74(5):2774-2790. doi: 10.1002/hep.31987.
13)Fang F, Cao W, Zhu W, Lam N,Li L, Gaddam S, Wang Y, Kim C, Lambert S, Zhang H, Hu B, Farber DL, Weyand CM, Goronzy JJ. The cell-surface 5'-nucleotidase CD73 defines a functional T memory cell subset that declines with age.Cell Reports. 2021 Nov 9;37(6):109981. doi: 10.1016/j.celrep.2021.109981.
14) Fang J, Ma Q, Chu C, Huang B,Li L, Cai P, Batista PJ, Tolentino KEM, Xu J, Li R, Du P, Qu K, Chang HY. PIRCh-seq: functional classification of non-coding RNAs associated with distinct histone modifications.Genome Biol. 2019; 20: 292.
15)Pattison JM, Melo SP, Piekos SN, Torkelson JL, Bashkirova E, Mumbach MR, Rajasingh C, Zhen HH,Li L, Liaw E, Alber D, Rubin AJ, Shankar G, Bao X, Chang HY, Khavari PA, Oro AE. Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment.Nature Genetics. 2018 Nov 5. doi: 10.1038/s41588-018-0263-0.
16)Batista PJ, Molinie B, Wang J, Qu K, Zhang J,Li L, Bouley DM, Lujan E, Haddad B, Daneshvar K, Carter AC, Flynn RA, Zhou C, Lim KS, Dedon P, Wernig M, Mullen AC, Xing Y, Giallourakis CC, Chang HY.
m6A RNA modification controls cell fate transition in mammalian embryonic stem cells.Cell Stem Cell. 2014 15 (6): 707-719.
17)SebastianoV, Zhen HH, Haddad B, Bashkirova E, Melo SP, Wang P, Leung TL, Siprashvili Z, Tichy A, Li J, Ameen M, Hawkins J, Lee S,Li L, Schwertschkow A, Bauer G, Lisowski L, Kay MA, Kim SK, Lane AT, Wernig M, Oro AE. Human COL7A1-corrected induced pluripotent stem cells for the treatment of recessive dystrophic epidermolysis bullosa.Science Translational Medicine.2014 6(264): 264ra163.
18)Yu H, He K,Li L, Sun L, Tang F, Li R, Ning W, Jin Y. Deletion of STK40 protein in mice causes respiratory failure and death at birth.Journal of Biological Chemistry.2013 288 (8), 5342-5352.
