Thymus medulla consisting of epithelial islets each derived from a single progenitor

Abstract

The thymus is organized into medullary and cortical zones that support distinct stages of T-cell development. The formation of medulla and cortex compartments is thought to occur through invagination of an endodermal epithelial sheet into an ectodermal one at the third pharyngeal pouch and cleft, respectively. Epithelial stem/progenitor cells have been proposed to be involved in thymus development, but evidence for their existence has been elusive. We have constructed chimaeric mice by injecting embryonic stem (ES) cells into blastocysts using ES cells and blastocysts differing in their major histocompatibility complex (MHC) type. Here we show that the MHC class-II-positive medullary epithelium in these chimaeras is composed of cell clusters, most of which derive from either embryonic stem cell or blastocyst, but not mixed, origin. Thus, the medulla comprises individual epithelial 'islets' each arising from a single progenitor. One thymic lobe has about 300 medullary areas that originate from as few as 900 progenitors. Islet formation can be recapitulated after implantation of 'reaggregated fetal thymic organs' into mice, which shows that medullary 'stem' cells retain their potential until at least day 16.5 in fetal development. Thus, medulla-cortex compartmentalization is established by formation of medullary islets from single progenitors.

Gene targeting of VEGF-A in thymus epithelium disrupts thymus blood vessel architecture

“…Tissue processing, cutting, staining for immunohistology, and photographic image processing were performed as described in ref. 24. The antibodies used, fluorochrome labelings, and concentrations are stated in Supporting Materials and Methods.…”

“…To determine the TEC origin by histology, MHC-mismatched chimeras were generated (24). (24,29) showed that both cortical and medullary cytokeratin ϩ cells were ES cell-derived (Fig.…”

A novel aspect of the structure of the avian thymic medulla

“…7a). In a cross-section, the epithelial cord and the club-shaped enlargements appear as islets embedded in mesenchyme (Rodewald 2008;Rodewald et al 2001) of neural crest origin. These experimental observations confirm the early histological findings, which described the thymic anlage as an epithelial island surrounded by mesenchyme (Maximov and Bloom 1938).…”

FGFR2IIIb signaling regulates thymic epithelial differentiation

“…Medullary TE contributes to the establishment of self-tolerance by presenting a wide array of self-antigens, participating in the elimination of self-reactive mature thymocytes and perhaps supporting further postselection maturation of these cells. There is continued postnatal maturation of the medullary TE compartment, where multiple medullary foci (Rodewald et al, 2001) expand and coalesce to form the complex medullary structure of the adult thymus (Anderson et al, 2000).…”