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Identification of fibroblast progenitors in the developing mouse thymus. 2022

Pedro Ferreirinha, and Ruben G R Pinheiro, and Jonathan J M Landry, and Nuno L Alves
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal.

The thymus stroma constitutes a fundamental microenvironment for T-cell generation. Despite the chief contribution of thymic epithelial cells, recent studies emphasize the regulatory role of mesenchymal cells in thymic function. Mesenchymal progenitors are suggested to exist in the postnatal thymus; nonetheless, an understanding of their nature and the mechanism controlling their homeostasis in vivo remains elusive. We resolved two new thymic fibroblast subsets with distinct developmental features. Whereas CD140αβ+GP38+SCA-1- cells prevailed in the embryonic thymus and declined thereafter, CD140αβ+GP38+SCA-1+ cells emerged in the late embryonic period and predominated in postnatal life. The fibroblastic-associated transcriptional programme was upregulated in CD140αβ+GP38+SCA-1+ cells, suggesting that they represent a mature subset. Lineage analysis showed that CD140αβ+GP38+SCA-1+ maintained their phenotype in thymic organoids. Strikingly, CD140αβ+GP38+SCA-1- generated CD140αβ+GP38+SCA-1+, inferring that this subset harboured progenitor cell activity. Moreover, the abundance of CD140αβ+GP38+SCA-1+ fibroblasts was gradually reduced in Rag2-/- and Rag2-/-Il2rg-/- thymi, indicating that fibroblast maturation depends on thymic crosstalk. Our findings identify CD140αβ+GP38+SCA-1- as a source of fibroblast progenitors and define SCA-1 as a marker for developmental stages of thymic fibroblast differentiation.

UI MeSH Term Description Entries
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013234 Stem Cells Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells. Colony-Forming Units,Mother Cells,Progenitor Cells,Colony-Forming Unit,Cell, Mother,Cell, Progenitor,Cell, Stem,Cells, Mother,Cells, Progenitor,Cells, Stem,Colony Forming Unit,Colony Forming Units,Mother Cell,Progenitor Cell,Stem Cell
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D013950 Thymus Gland A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat. Thymus,Gland, Thymus,Glands, Thymus,Thymus Glands
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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