Transdifferentiation of parathyroid cells into cervical thymi promotes atypical T-cell development

Abstract

The thoracic thymus is the primary vertebrate organ for T cell generation. Accessory cervical thymi have also been identified in humans and mice, and shown in mice to be independent functional organs that support T cell development. However, their origin and functional significance remain unclear. Here we show that cervical thymi in mice have two origins: delayed differentiation of endodermal precursors, and transdifferentiation of parathyroid-fated cells. Compared to thoracic thymus, parathyroid-origin cervical thymi (pCT) express low levels of the thymic epithelial cell-specific transcription factor FOXN1. Consequently, pCT form a distinct microenvironment that supports an atypical thymocyte development pathway, generating T cells with unconventional phenotypic characteristics. Our data demonstrate a transdifferentiation origin for a subset of cervical thymi, with specific functional consequences for T cell development.