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科學研究

陳婷博士

陳婷博士

北京生命科學研究所高級研究員

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

Phone：86-10-80726688

Fax： 86-10-80726689

E-mail：chenting@nibs.ac.cn

本研究組主要從事組織再生調控與疾病發生機制的研究，重點研究皮膚微環境在組織再生過程中調控干細胞命運決定的生物學功能和分子機理，以及闡明遺傳性或獲得性皮膚疾病的致病機制，為疾病治療提供新的方向。我們的工作主要包括以下三個方向：

1. 皮膚微環境調控組織再生與衰退的機制

人體的皮膚會面臨終其一生的磨損與消耗，為維持組織穩態平衡與正常功能，皮膚是成體中為數不多具有強大再生能力的器官。皮膚再生能力主要依賴于三種不同的成體干細胞：毛囊干細胞、黑色素干細胞和表皮干細胞，分別支持毛發、色素以及表皮的再生與修復。這三類成體干細胞在體內的功能都受微環境的調控，組織內微環境細胞的類型復雜，異質性高，在不同生理與病理條件下微環境信號的動態變化在組織再生、損傷修復和疾病發生過程中都起到重要作用, 因此解析微環境調控干細胞命運的細胞分子機制是再生領域核心的科學問題，也是再生醫學與相關疾病研究的基礎。我們課題組將利用細胞特異性遺傳譜系追蹤、活體成像、體內遺傳篩選、光遺傳學等技術手段，從細胞與分子水平闡明皮膚微環境細胞的異質性與可塑性，解析微環境通過生物大分子、代謝小分子、以及物理特性調控干細胞命運決定、自我更新、激活以及衰變的機制。

2.皮膚區域特異性在物種演變、個體水平組織再生、以及疾病發生過程中的作用機制

皮膚不但有屏障功能，而且有重要的感知與調控功能，比如視覺偽裝，觸覺感知，溫度調控，與微生物免疫互作等，這一系列重要功能由皮膚里的微小器官和特異細胞類型完成，包括皮膚附屬物毛發、汗腺、皮脂腺、機械力感應細胞、免疫細胞、神經末梢等。皮膚作為生物體面積最大的器官，這些功能迥異的細胞類型以及微小器官都具有獨特的區域特異性，并在進化過程中演變出物種差異，對個體的生存至關重要。除了正常生理條件，許多皮膚疾病也有鮮明的區域特異性，一部分特征甚至成為臨床診斷指標。這些現象表明編碼皮膚區域特異性的“郵政編碼”體系在物種演變、個體水平的器官發育與組織再生、以及疾病發生過程中都起到了重要作用。但是到目前為止，我們對于編碼皮膚區域特異性的細胞分子基礎、物種間區域性皮膚功能演變的機理、以及區域性皮膚疾病的致病基礎這幾方面的認識還相當有限。我們課題組結合細胞生物學、遺傳學、發育生物學和分子生物學技術，系統地研究染色質高級結構調控Hoxc區域表達的機理、不同區域微環境細胞異質性的差異、物種間區域性再生能力差異的分子基礎、以及決定區域性皮膚疾病發生的的細胞分子機制。

3. 調控免疫豁免以及自身免疫性皮膚疾病的細胞分子機理

作為隔絕自我與外界的第一道物理屏障，皮膚內的上皮細胞與免疫細胞在正常生理情況下就會頻繁接觸非己的細菌病毒等微生物，而且皮膚內本身就包含具有重要功能的死細胞與非活性結構，因此皮膚面臨區分我與非我的根本生物學問題。很多常見的后天獲得性皮膚自身免疫性疾病比如白癜風、斑禿等，就是自體免疫細胞異常激活后攻擊皮膚內的黑色素細胞或毛囊的后果，這些常見疾病在臨床癥狀上雖然有明顯共性，但是因為疾病誘因復雜，并且通常缺乏有效的疾病模型，因此未能得到深入的機制研究，闡明皮膚自身免疫疾病發生的細胞分子機理是開發有效治療方法的前提。我們課題組主要采用建立小鼠疾病模型，結合遺傳學、分子生物學、細胞生物學等技術研究皮膚免疫豁免的細胞分子基礎，以及自身免疫疾病的發病機理，為疾病治療提供新方向。

本實驗室常年招聘博士后，待遇從優。歡迎博士生、碩士生、本科生報考和實習。

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.