title: Adult thymus contains FoxN1(-) epithelial stem cells that are bipotent for medullary and cortical thymic epithelial lineages.
abstract: Within the thymus, two major thymic epithelial cell (TEC) subsets-cortical and medullary TECs-provide unique structural and functional niches for T cell development and establishment of central tolerance. Both lineages are believed to originate from a common progenitor cell, yet the cellular and molecular identity of these bipotent TEC progenitors/stem cells remains ill defined. Here we identify rare stromal cells in the murine adult thymus, which under low-attachment conditions formed spheres (termed "thymospheres"). These thymosphere-forming cells (TSFCs) displayed the stemness features of being slow cycling, self-renewing, and bipotent. TSFCs could be significantly enriched based on their distinct surface antigen phenotype. The FoxN1 transcription factor was dispensable for TSFCs maintenance in situ and for commitment to the medullary and cortical TEC lineages. In summary, this study presents the characterization of the adult thymic epithelial stem cells and demonstrates the dispensability of FoxN1 function for their stemness.
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Cellular Senescence Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ucar
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Ucar
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Klug
authors.affiliation: Cellular Senescence Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Matt
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Brunk
authors.affiliation: Cellular Senescence Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany. Electronic address: t.hofmann@dkfz.de.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: b.kyewski@dkfz.de.
authors.forename: Bruno
authors.initials: B
authors.lastname: Kyewski
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D051927:CD24 Antigen / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D002478:Cells, Cultured; D002675:Child, Preschool; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009924:Organ Culture Techniques; D013234:Stem Cells / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
chemical_list: D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D051927:CD24 Antigen; C497890:Cd24a protein, mouse; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D051858:Forkhead Transcription Factors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C090140:Whn protein; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse