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nature portfolio privacy policy elisa commercial kits nature advertising open cycle kind offering anti-mts15 mab social media cdna library bone marrow-derived fibrocytes specific pathogen-free conditions 0/ reprints medical research middle cd45−epcam+uea-1+aire+ cells cytoplasmic calcium-binding proteins alexa fluor® 610—r-phycoerythrin anti-cd45-percp/cy5 fsp-gfp reporter mice collagenase/dispase enzyme mixture research gated cd45−epcam+ cells fsp1-gfp reporter mice33 fsp1-thymidine kinase fibroblast-derived cell subset thymic cd45-fsp1+ cells thymic cd45−fsp1+ cells gated cd45−fsp1+ cells hematopoietic cd45−fsp1+ cells hematopoietic-derived fsp1+ cells thymic cd45−fsp1− fibroblasts thymic cd45−fsp1+ fibroblasts key direct regulator flt3 ligand-receptor interaction cortical epithelial cells single-cell transcriptional profiling double-transgenic mice defined fsp1-gfp+ thymic fibroblasts thymic fsp1-gfp− fibroblasts induce thymus atrophy anti-cd8-pe/cy5 full size image gcv-treated fsp1-tk mice fsp1-gfp reporter mice real-time pcr assay neural crest-derived cells peripheral t-cell reconstitution oct-embedded frozen tissues establish t-cell tolerance cd45−epcam+uae-1+ mtecs

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         headline:FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells
         description: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 (MHCIIhigh, 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.
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      description: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 (MHCIIhigh, 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.
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