title: FSP1(+) fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells.
abstract: Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45(-)FSP1(+) cells represent a unique Fibroblast specific protein 1 (FSP1)(-)fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCII(high), CD80(+) and Aire(+)). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45(-)FSP1(+) fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1(+) fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1(-) counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45(-)FSP1(+) cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Chenming
authors.initials: C
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhanfeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongran
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Pengbo
authors.initials: P
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003520:Cyclophosphamide / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005333:Fetus; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D012038:Regeneration / Q000502:physiology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics*; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: C496454:Fgf7 protein, mouse; D015850:Interleukin-6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C577686:interleukin-6, mouse; D051523:Fibroblast Growth Factor 7; D003520:Cyclophosphamide; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse