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Cell Rep. 2016 Oct 4;17(2):448-457. doi: 10.1016/j.celrep.2016.09.027.

A Thymic Epithelial Stem Cell Pool Persists throughout Ontogeny and Is Modulated by TGF-β.

Author information

1
Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: olga.ucar@alumni.dkfz.de.
2
Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
3
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.
4
Center for Biological Systems Analysis (ZBSA), BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
5
Division of Epigenetics, Cellular Senescence Group, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
6
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.
7
Division of Developmental Immunology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: b.kyewski@dkfz.de.

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.

KEYWORDS:

FoxN1; stem cells; thymic epithelium; thymosphere; thymus

PMID:
27705793
PMCID:
PMC5067280
DOI:
10.1016/j.celrep.2016.09.027
[Indexed for MEDLINE]
Free PMC Article

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