title: Long-term persistence of functional thymic epithelial progenitor cells in vivo under conditions of low FOXN1 expression.
abstract: 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.
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, United Kingdom.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, United Kingdom.
authors.forename: Craig S
authors.initials: CS
authors.lastname: Nowell
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, United Kingdom.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Ulyanchenko
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, United Kingdom.
authors.forename: Frances H
authors.initials: FH
authors.lastname: Stenhouse
authors.affiliation: MRC Centre for Regenerative Medicine, Institute for Stem Cell Research, School of Biological Sciences, University of Edinburgh, SCRM Building, 5 Little France Drive, Edinburgh, EH16 4UU, United Kingdom.
authors.forename: C Clare
authors.initials: CC
authors.lastname: Blackburn
mesh_terms: D000483:Alleles; D000818:Animals; D004847:Epithelial Cells / Q000166:cytology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011257:Pregnancy Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism / Q000473:pathology
chemical_list: D051858:Forkhead Transcription Factors; C526395:Plet-1 protein, mouse; D011257:Pregnancy Proteins; C090140:Whn protein; D007633:Keratins