陈婷博士

科学研究

陈婷博士

北京生命科学研究所高级研究员

Ting Chen, Ph.D. Associate Investigator, NIBS, Beijing，China

Phone：86-10-80726688

Fax： 86-10-80726689

E-mail：chenting@nibs.ac.cn

本研究组主要从事组织再生调控与疾病发生机制的研究，重点研究皮肤微环境在组织再生过程中调控干细胞命运决定的生物学功能和分子机理，以及阐明遗传性或获得性皮肤疾病的致病机制，为疾病治疗提供新的方向。我们的工作主要包括以下三个方向：

1. 皮肤微环境调控组织再生与衰退的机制

人体的皮肤会面临终其一生的磨损与消耗，为维持组织稳态平衡与正常功能，皮肤是成体中为数不多具有强大再生能力的器官。皮肤再生能力主要依赖于三种不同的成体干细胞：毛囊干细胞、黑色素干细胞和表皮干细胞，分别支持毛发、色素以及表皮的再生与修复。这三类成体干细胞在体内的功能都受微环境的调控，组织内微环境细胞的类型复杂，异质性高，在不同生理与病理条件下微环境信号的动态变化在组织再生、损伤修复和疾病发生过程中都起到重要作用, 因此解析微环境调控干细胞命运的细胞分子机制是再生领域核心的科学问题，也是再生医学与相关疾病研究的基础。我们课题组将利用细胞特异性遗传谱系追踪、活体成像、体内遗传筛选、光遗传学等技术手段，从细胞与分子水平阐明皮肤微环境细胞的异质性与可塑性，解析微环境通过生物大分子、代谢小分子、以及物理特性调控干细胞命运决定、自我更新、激活以及衰变的机制。

2.皮肤区域特异性在物种演变、个体水平组织再生、以及疾病发生过程中的作用机制

皮肤不但有屏障功能，而且有重要的感知与调控功能，比如视觉伪装，触觉感知，温度调控，与微生物免疫互作等，这一系列重要功能由皮肤里的微小器官和特异细胞类型完成，包括皮肤附属物毛发、汗腺、皮脂腺、机械力感应细胞、免疫细胞、神经末梢等。皮肤作为生物体面积最大的器官，这些功能迥异的细胞类型以及微小器官都具有独特的区域特异性，并在进化过程中演变出物种差异，对个体的生存至关重要。除了正常生理条件，许多皮肤疾病也有鲜明的区域特异性，一部分特征甚至成为临床诊断指标。这些现象表明编码皮肤区域特异性的“邮政编码”体系在物种演变、个体水平的器官发育与组织再生、以及疾病发生过程中都起到了重要作用。但是到目前为止，我们对于编码皮肤区域特异性的细胞分子基础、物种间区域性皮肤功能演变的机理、以及区域性皮肤疾病的致病基础这几方面的认识还相当有限。我们课题组结合细胞生物学、遗传学、发育生物学和分子生物学技术，系统地研究染色质高级结构调控Hoxc区域表达的机理、不同区域微环境细胞异质性的差异、物种间区域性再生能力差异的分子基础、以及决定区域性皮肤疾病发生的的细胞分子机制。

3. 调控免疫豁免以及自身免疫性皮肤疾病的细胞分子机理

作为隔绝自我与外界的第一道物理屏障，皮肤内的上皮细胞与免疫细胞在正常生理情况下就会频繁接触非己的细菌病毒等微生物，而且皮肤内本身就包含具有重要功能的死细胞与非活性结构，因此皮肤面临区分我与非我的根本生物学问题。很多常见的后天获得性皮肤自身免疫性疾病比如白癜风、斑秃等，就是自体免疫细胞异常激活后攻击皮肤内的黑色素细胞或毛囊的后果，这些常见疾病在临床症状上虽然有明显共性，但是因为疾病诱因复杂，并且通常缺乏有效的疾病模型，因此未能得到深入的机制研究，阐明皮肤自身免疫疾病发生的细胞分子机理是开发有效治疗方法的前提。我们课题组主要采用建立小鼠疾病模型，结合遗传学、分子生物学、细胞生物学等技术研究皮肤免疫豁免的细胞分子基础，以及自身免疫疾病的发病机理，为疾病治疗提供新方向。

本实验室常年招聘博士后，待遇从优。欢迎博士生、硕士生、本科生报考和实习。

Publications:

29. Guo S, Liu C, Xu Y, Wang X, Nan F, Huang Y, Li S, Nan S, Li L, Edo Kon, Li C,Wei M, Su R, Wei J, Peng S, Nitay Ad-El, Liu J, Dan Peer, Chen T, Yang L, Chen L*. Therapeutic application of circular RNA aptamers in a mouse model of psoriasis. Nature Biotechnology. 2024. Doi: 10.1038/s41587-024-02204-4.

28. Du Y, Qi X, Zhang L,Yang Y, Chen T*. Calcium influx-induced lytic cell death disrupts skin immune homeostasis. Cell Discovery. 2023; 9:124. DOI:10.1038/s41421-023-00623-2.

27. Zhang B*, Chen T*. Local and systemic mechanisms that control the hair follicle stem cell niche. Nature Reviews Molecular Cell Biology. 2023. DOI: 10.1038/s41580-023-00662-3.

26. Su R, Huang H, Chang Y, Yu Y, Cui J, Chen T*, Li B*, Wang W*. Mosaic somatic HRAS mutation causes unilateral psoriasis. Life Medicine. 2023. DOI: 10.1093/lifemedi/lnad018.

25. Chen D^#, Xu Z^#, Cui J, Chen T*. A mouse model of vitiligo based on endogenous auto-reactive CD8+ T cell targeting skin melanocyte. Cell Regen. 2022;11(1):31. DOI: 10.1186/s13619-022-00132-9.

24. Xie Y, Chen T*. Mouse tail skin wholemount staining and intravital calcium imaging. STAR Protocols. 2022;3(1):101235. DOI: 10.1016/j.xpro.2022.101235.

23. Xu Z^#, Chen D^#, Hu Y, Jiang K, Huang H, Du Y, Wu W, Wang J, Sui J, Wang W, Zhang L, Li S, Li C, Yong Y, Chang J*, Chen T*. Anatomically distinct fibroblast subsets determine skin autoimmune patterns. Nature. 2022;601(7891):118-124. DOI: 10.1038/s41586-021-04221-8.

• Recommended by Faculty Member Thierry Passeron at Faculty Opinions as Exceptional, Faculty Opinions. 2022; 10.3410/f.741322615.793590880.

22. Xie Y, Chen D, Jiang K, Song L, Qian N, Du Y, Yang Y, Wang F, Chen T*. Hair shaft miniaturization causes stem cell depletion through mechano-sensory signals mediated by a Piezo1-calcium-TNFα axis. Cell Stem Cell. 2022;29(1):70-85.e6. DOI: 10.1016/j.stem.2021.09.009.

• Research Highlight by Paulina Strzyz. Compression as a driver of hair loss. Nat Rev Mol Cell Biol. 2021;22(12):775. DOI: 10.1038/s41580-021-00426-x.

• Preview by Terry Lechler. Hair follicle stem cells feel the pressure. Cell Stem Cell. 2022;29(1):1-2. DOI:https://doi.org/10.1016/j.stem.2021.12.001.

21. Song Z, Chen X, Zhao Q, Stanic V, Lin Z, Yang S, Chen T, Chen J, Yang Y*. Hair loss caused by gain-of-function mutant TRPV3 is associated with premature differentiation of follicular keratinocytes. J Invest Dermatol. 2021;S0022-202X(21)00158-5. DOI: 10.1016/j.jid.2020.11.036.

20. Zou Z, Long X, Zhao Q, Zheng Y, Song M, Ma S, Jing Y, Wang S, He Y, Esteban CR, Yu N, Huang J, Chan P, Chen T, Izpisua Belmonte JC, Zhang W, Qu J, Liu GH*. A Single-Cell Transcriptomic Atlas of Human Skin Aging. Developmental Cell. 2021;56(3):383-397.e8. DOI: 10.1016/j.devcel.2020.11.002.

19. Lu Z, Xie Y, Huang H, Jiang K, Zhou B, Wang F, Chen T*. Hair follicle stem cells regulate retinoid metabolism to maintain the self-renewal niche for melanocyte stem cells. eLife. 2020;9:e52712. DOI: 10.7554/eLife.52712.

18. Li F, Lu Z, Wu W, Qian N, Wang F, Chen T*. Optogenetic gene editing in regional skin. Cell Research. 2019;29(10):862-865. DOI: 10.1038/s41422-019-0209-9.

17. Wu W, Chen T*. Ribonucleoproteins Mediated Efficient In Vivo Gene Editing in Skin Stem Cells. Methods Mol Biol. 2019;1879:75-86. DOI: 10.1007/7651_2018_115.

16. Yu Z, Jiang K, Xu Z, Huang H, Qian N, Lu Z, Chen D, Di R, Yuan T, Du Z, Xie W, Lu X, Li H, Chai R, Yang Y, Zhu B, Kunieda T, Wang F*, Chen T*. Hoxc-Dependent Mesenchymal Niche Heterogeneity Drives Regional Hair Follicle Regeneration. Cell Stem Cell. 2018;23(4):487-500.e6. DOI: 10.1016/j.stem.2018.07.016.

• Featured free article with cover

• Preview by SE. Millar. Hox in the Niche Controls Hairy-geneity.Cell Stem Cell. 2018;23(4):457-458. DOI: 10.1016/j.stem.2018.09.012.

15. Fan SM, Chang YT, Chen CL, Wang WH, Pan MK, Chen WP, Huang WY, Xu Z, Huang HE, Chen T, Plikus MV, Chen SK, Lin SJ*. External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway. PNAS. 2018;115(29):E6880-E6889. DOI: 10.1073/pnas.1719548115.

14. Nguyen MB, Cohen I, Kumar V, Xu Z, Bar C, Dauber-Decker KL, Tsai PC, Marangoni P, Klein OD, Hsu YC, Chen T, Mikkola ML, Ezhkova E*. FGF signalling controls the specification of hair placode-derived SOX9 positive progenitors to Merkel cells. Nature Communications. 2018;9(1):2854. DOI: 10.1038/s41467-018-04399-y.

13. Wu W, Lu Z, Li F, Wang W, Qian N, Duan J, Zhang Y, Wang F, Chen T*. Efficient in vivo gene editing using ribonucleoproteins in skin stem cells of recessive dystrophic epidermolysis bullosa mouse model. PNAS. 2017;114(7):1660-1665. DOI: 10.1073/pnas.1614775114.

• Selected by The Latest Science “ Paper of the Year ”

• News report by Epidermolysis Bullosa News

12. Yu Z, Chen T*. Regional differences: The skin is a complex landscape containing regions in which hair follicles exhibit different types of behavior. eLife. 2017;6: e30249. DOI: 10.7554/eLife.30249.

11. He L, Li Y, Li Y, Pu W, Huang X, Tian X, Wang Y, Zhang H, Liu Q, Zhang L, Zhao H, Tang J, Ji H, Cai D, Han Z, Han Z, Nie Y, Hu S, Wang QD, Sun R, Fei J, Wang F, Chen T, Yan Y, Huang H, Pu WT, Zhou B*. Enhancing the precision of genetic lineage tracing using dual recombinases. Nature Medicine. 2017;23(12):1488-1498. DOI: 10.1038/nm.4437.

10. Zhang H, Huang X, Liu K, Tang J, He L, Pu W, Liu Q, Li Y, Tian X, Wang Y, Zhang L, Yu Y, Wang H, Hu R, Wang F, Chen T, Wang QD, Qiao Z, Zhang L, Lui KO, Zhou B*. Fibroblasts in an endocardial fibroelastosis disease model mainly originate from mesenchymal derivatives of epicardium. Cell Research. 2017;27(9):1157-1177. DOI: 10.1038/cr.2017.103.

9. He L, Huang X, Kanisicak O, Li Y, Wang Y, Li Y, Pu W, Liu Q, Zhang H, Tian X, Zhao H, Liu X, Zhang S, Nie Y, Hu S, Miao X, Wang QD, Wang F, Chen T, Xu Q, Lui KO, Molkentin JD, Zhou B*. Preexisting endothelial cells mediate cardiac neovascularization after injury. J Clin Invest. 2017;127(8):2968-2981. DOI: 10.1172/JCI93868.

8. Lin Z, Li S, Feng C, Yang S, Wang H, Ma D, Zhang J, Gou M, Bu D, Zhang T, Kong X, Wang X, Sarig O, Ren Y, Dai L, Liu H, Zhang J, Li F, Hu Y, Padalon-Brauch G, Vodo D, Zhou F, Chen T, Deng H, Sprecher E, Yang Y*, Tan X*. Stabilizing mutations of KLHL24 ubiquitin ligase cause loss of keratin 14 and human skin fragility. Nature Genetics. 2016;48(12):1508-1516. DOI: 10.1038/ng.3701.

7. Xu Z, Wang W, Jiang K, Yu Z, Huang H, Wang F, Zhou B, Chen T*. Embryonic attenuated Wnt/β-catenin signaling defines niche location and long-term stem cell fate in hair follicle. eLife. 2015;4:e10567. DOI: 10.7554/eLife.10567.

6. Deng Z, Lei X, Zhang X, Zhang H, Liu S, Chen Q, Hu H, Wang X, Ning L, Cao Y, Zhao T, Zhou J, Chen T, Duan E*. mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration. J MOL CELL BIOL. 2015;7(1):62-72. DOI: 10.1093/jmcb/mjv005.

5. Fuchs E*, Chen T. A matter of life and death: self-renewal in stem cells. EMBO Rep. 2013;14(1):39-48. DOI: 10.1038/embor.2012.197.

4. Chen T, Heller E, Beronja S, Oshimori N, Stokes N, Fuchs E*. An RNA interference screen uncovers a new molecule in stem cell self-renewal and long-term regeneration. Nature. 2012;485(7396):104-8. DOI: 10.1038/nature10940.

• Selected by Faculty of 1000 Biology

3. Greco V^#, Chen T^#, Rendl M, Schober M, Pasolli HA, Stokes N, Dela Cruz-Racelis J, Fuchs E*. A two-step mechanism for stem cell activation during hair regeneration. Cell Stem Cell. 2009;6;4(2):155-69. DOI: 10.1016/j.stem.2008.12.009.

• Authors contributed equally

• Highlight Review in Cell Stem Cell

• Selected by Faculty of 1000 Biology

2. Chen T, Muratore TL, Schaner-Tooley CE, Shabanowitz J, Hunt DF, Macara IG*. N-terminal α-methylation of RCC1 is necessary for stable chromatin association and normal mitosis. Nat Cell Biol. 2007;9(5):596-603. DOI: 10.1038/ncb1572.

• Highlight Review in Nature Cell Biology

• Selected by Faculty of 1000 Biology

1. Chen T, Brownawell AM, Macara IG*. Nucleocytoplasmic Shuttling of JAZ, a New Cargo Protein for Exportin-5. Mol Cell Biol. 2004;24(15):6608-19. DOI: 10.1038/ncb1572.