Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression

Normal thymus function reflects interactions between developing T-cells and several thymic stroma cell types. Within the stroma, key functions reside in the distinct cortical and medullary thymic epithelial cell (TEC) types. It has been demonstrated that, during organogenesis, all TECs can be derive...

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Bibliographic Details
Published in:PloS one 2014-12, Vol.9 (12), p.e114842-e114842
Main Authors: Jin, Xin, Nowell, Craig S, Ulyanchenko, Svetlana, Stenhouse, Frances H, Blackburn, C Clare
Format: Article
Language:English
Subjects:
Alleles
Animals
Biology and Life Sciences
Cells (biology)
Cortex
Epithelial cells
Epithelial Cells - cytology
Female
Forkhead Transcription Factors - genetics
Forkhead Transcription Factors - metabolism
Genotype
Genotype & phenotype
Immunohistochemistry
In vivo methods and tests
Keratins - metabolism
Lymphocytes
Lymphocytes T
Male
Medical research
Medicine
Mice
Mice, Inbred BALB C
Mice, Knockout
Organogenesis
Pregnancy Proteins - metabolism
Progenitor cells
Rodents
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stroma
T cells
Thymus
Thymus Gland - cytology
Thymus Gland - metabolism
Thymus Gland - pathology
Transcription factors
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Summary:Normal thymus function reflects interactions between developing T-cells and several thymic stroma cell types. Within the stroma, key functions reside in the distinct cortical and medullary thymic epithelial cell (TEC) types. It has been demonstrated that, during organogenesis, all TECs can be derived from a common thymic epithelial progenitor cell (TEPC). The properties of this common progenitor are thus of interest. Differentiation of both cTEC and mTEC depends on the epithelial-specific transcription factor FOXN1, although formation of the common TEPC from which the TEC lineage originates does not require FOXN1. Here, we have used a revertible severely hypomorphic allele of Foxn1, Foxn1R, to test the stability of the common TEPC in vivo. By reactivating Foxn1 expression postnatally in Foxn1R/- mice we demonstrate that functional TEPCs can persist in the thymic rudiment until at least 6 months of age, and retain the potential to give rise to both cortical and medullary thymic epithelial cells (cTECs and mTECs). These data demonstrate that the TEPC-state is remarkably stable in vivo under conditions of low Foxn1 expression, suggesting that manipulation of FOXN1 activity may prove a valuable method for long term maintenance of TEPC in vitro.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0114842