TY  - JOUR
AU  - Brunk, Fabian
AU  - Michel, Chloé
AU  - Holland-Letz, Tim
AU  - Slynko, Alla
AU  - Kopp-Schneider, Annette
AU  - Kyewski, Bruno
AU  - Pinto, Sheena
TI  - Dissecting and modeling the emergent murine TEC compartment during ontogeny.
JO  - European journal of immunology
VL  - 47
IS  - 7
SN  - 0014-2980
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2017-01415
SP  - 1153 - 1159
PY  - 2017
AB  - The origin of the thymic epithelium, i.e. the cortical (cTEC) and medullary (mTEC) epithelial cells, from bipotent stem cells through TEC progenitors and lineage-specific progeny still remains poorly understood. We sought to obtain an unbiased view of the incipient emergence of TEC subsets by following embryonic TEC development based on co-expression of EpCAM, CD80 and MHC class II (MHCII) on non-hematopoietic (CD45(-) ) thymic stromal cells in wild-type BL6 mice. Using a combination of ex vivo analysis, Re-aggregate Thymic Organ Culture (RTOC) reconstitution assays and mathematical modeling, we traced emergent lineage commitment in murine embryonic TECs. Both experimental and mathematical datasets supported the following developmental sequence: MHCII(-) CD80(-) → MHCII(lo) CD80(-) → MHCII(hi) CD80(-) → MHCII(hi) CD80(hi) TECs, whereby MHCII(hi) CD80(-) and MHCII(hi) CD80(hi) TECs bear features of cTECs and mTECs respectively. These emergent MHCII(hi) CD80(-) cTECs directly generate mature MHCII(hi) CD80(hi) mTECs in vivo and in vitro, thus supporting the asynchronous model of TEC lineage commitment.
LB  - PUB:(DE-HGF)16
C6  - pmid:28439878
DO  - DOI:10.1002/eji.201747006
UR  - https://inrepo02.dkfz.de/record/125276
ER  -