A novel Foxn1eGFP/+ mouse model identifies Bmp4‐induced maintenance of Foxn1 expression and thymic epithelial progenitor populations. Issue 2 (7th December 2016)

• Record Type: Journal Article
• Authors: Barsanti, Marco; Lim, Joanna M. C.; Hun, Michael L.; Lister, Natalie; Wong, Kahlia; Hammett, Maree V.; Lepletier, Ailin; Boyd, Richard L.; Giudice, Antonietta; Chidgey, Ann P.
• Is Part Of: European journal of immunology. Volume 47:Issue 2(2017)
• Page Start: 291
• Page End: 304
• Publication Date: 2016-12-07
• Subjects: Aging -- Bmp4 -- Foxn1 -- Foxn1eGFP mouse model -- Thymic epithelial cell -- Thymic epithelial progenitor cell -- Thymus development; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201646553
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract : Using our Foxn1 eGFP/+ knock‐in mouse model, we confirmed the negative association between aging and Foxn1 expression in thymic epithelial cells (TEC). We also show that Bmp4 supplementation improved in vitro maintenance of thymic epithelial progenitor cells (TEPC) and enhanced their Foxn1 expression. Abstract : Although forkhead‐box n1 (Foxn1) is a critical thymic epithelial cell regulator in thymus organogenesis, its association with epithelial differentiation and homeostasis in the postnatal and aged thymic microenvironment remains conflicting. Consequently, we have generated a Foxn1 eGFP/+ knock‐in mouse model that allows for refined investigation of the aging thymic epithelium. This reporter line differs from those previously published in that concomitant expression of enhanced green fluorescent protein enables live cell sorting of Foxn1 + cell populations. Our heterozygotes did not exhibit haploinsufficiency, with Foxn1 expression resembling that of wild‐type mice. Comparative analysis between Foxn1 and enhanced green fluorescent protein at both the transcriptional and translational levels revealed co‐localization, with progressive down‐regulation observed predominantly in the aging cortical epithelium. Supplementation with bone morphogenetic protein (Bmp)‐4 enhanced Foxn1 expression and colony forming efficiency in both embryonic and adult progenitor 3D cultures. Strikingly, selective maintenance of immature cortical and medullary epithelial cells was observed which is consistent with the higher Bmp receptor 2 expression levels seen in these progenitor populations. This study demonstrates the significance of our mouse model in unraveling the role of this master regulator in thymus development, homeostasis and aging, providing a faithful reporter system for phenotypic and functional investigations.