The transcription factor FOXN1 is essential for fetal thymic epithelial cell (TEC) differentiation and proliferation. Postnatally, Foxn1 levels vary widely between TEC subsets, from low/undetectable in putative TEC progenitors to highest in differentiated TEC subsets. Correct Foxn1 expression is required to maintain the postnatal microenvironment; premature down-regulation of Foxn1 causes a rapid involution-like phenotype, while transgenic over-expression can cause thymic hyperplasia and/or delayed involution. We investigated a K5.Foxn1 transgene that drives over-expression in TECs, but neither causes hyperplasia, nor delays or prevents aging-related involution. Similarly, this transgene cannot rescue thymus size in Foxn1lacZ/lacZmice that undergo premature involution due to reduced Foxn1 levels. However, K5.Foxn1 transgenics do maintain TEC differentiation and cortico-medullary organization with aging, both alone and in Foxn1lacZ/lacZ mice. Analysis of candidate TEC markers showed co-expression of progenitor and differentiation markers as well as increased proliferation in Plet-1+ TECs associated with Foxn1 expression. These results demonstrate that the functions of FOXN1 in promoting TEC proliferation and differentiation are separable and context-dependent, and suggest that modulating Foxn1 levels can regulate the balance of proliferation and differentiation in TEC progenitors.
Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution
Present address: Department of Pathology, Duke University Medical Center, Durham, NC, USA
- Award Group:
- Funder(s): NIH
- Award Id(s): P01AG052359-01A1
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Jie Li, Lucas P. Wachsmuth, Shiyun Xiao, Brian G. Condie, Nancy R. Manley; Foxn1 overexpression promotes thymic epithelial progenitor cell proliferation and mTEC maintenance, but does not prevent thymic involution. Development 2023; dev.200995. doi: https://doi.org/10.1242/dev.200995
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