title: A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated by TGF-β.
abstract: Adult tissue-specific stem cells (SCs) mediate tissue homeostasis and regeneration and can give rise to all lineages in the corresponding tissue, similar to the early progenitors that generate organs in the first place. However, the developmental origins of adult SCs are largely unknown. We recently identified thymosphere-forming stem cells (TSFCs) in the adult mouse thymus, which display genuine stemness features and can generate the two major thymic epithelial cell lineages. Here, we show that embryonic TSFCs possess stemness features but differ from adult TSFCs in surface marker profile. Our findings support the model of a continuous thymic SC lineage that is maintained throughout ontogeny. TGF-β signaling differentially affects embryonic versus adult thymosphere formation, suggesting that thymic epithelial SC potency depends on both developmental stage and environmental signals. Collectively, our findings suggest that embryonic TSFCs contribute to an adult SC pool and that TSFC plasticity is controlled by TGF-β signaling.
authors.affiliation: Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: olga.ucar@alumni.dkfz.de.
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: Kaiyong
authors.initials: K
authors.lastname: Li
authors.affiliation: Division of Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
authors.forename: Dmytro
authors.initials: D
authors.lastname: Dvornikov
authors.affiliation: Center for Biological Systems Analysis (ZBSA), BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kreutz
authors.affiliation: Center for Biological Systems Analysis (ZBSA), BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Timmer
authors.affiliation: Division of Epigenetics, 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: Lukas
authors.initials: L
authors.lastname: Brenner
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, Wellcome Trust Centre for Cell-Matrix Research, Manchester M13 9NT, UK; Manchester Immunology Group, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: Smedley
authors.affiliation: Manchester Collaborative Centre for Inflammation Research, Wellcome Trust Centre for Cell-Matrix Research, Manchester M13 9NT, UK; Manchester Immunology Group, University of Manchester, Manchester M13 9NT, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Travis
authors.affiliation: Division of Epigenetics, Cellular Senescence Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
authors.affiliation: Division of Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Translational Lung Research Center (TLRC) Heidelberg, German Center for Lung Research (DZL), 69120 Heidelberg, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Klingmüller
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; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction; D013950:Thymus Gland / Q000166:cytology* / Q000254:growth & development; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D016212:Transforming Growth Factor beta
keywords: FoxN1; stem cells; thymic epithelium; thymosphere; thymus