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Recent work has shown that gene-expression patterns within the mTEC compartment are heterogenous and include multiple differentiated cell states. To further define mTEC development and medullary epithelial lineage relationships, we combined lineage tracing and recovery from transient in vivo mTEC ablation with single-cell RNA-sequencing in\n                    <jats:italic>Mus musculus<\/jats:italic>\n                    . The combination of bioinformatic and experimental approaches revealed a non-stem transit-amplifying population of cycling mTECs that preceded\n                    <jats:italic>Aire<\/jats:italic>\n                    expression. We propose a branching model of mTEC development wherein a heterogeneous pool of transit-amplifying cells gives rise to\n                    <jats:italic>Aire<\/jats:italic>\n                    - and\n                    <jats:italic>Ccl21a<\/jats:italic>\n                    -expressing mTEC subsets. We further use experimental techniques to show that within the\n                    <jats:italic>Aire-<\/jats:italic>\n                    expressing developmental branch, TSA expression peaked as\n                    <jats:italic>Aire<\/jats:italic>\n                    expression decreased, implying\n                    <jats:italic>Aire<\/jats:italic>\n                    expression must be established before TSA expression can occur. Collectively, these data provide a roadmap of mTEC development and demonstrate the power of combinatorial approaches leveraging both in vivo models and high-dimensional datasets.\n                  <\/jats:p>","DOI":"10.7554\/elife.60188","type":"journal-article","created":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T09:10:35Z","timestamp":1606122635000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.60188","source":"Crossref","is-referenced-by-count":96,"title":["Combined transient ablation and single-cell RNA-sequencing reveals the development of medullary thymic epithelial cells"],"prefix":"10.7554","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7466-8164","authenticated-orcid":true,"given":"Kristen L","family":"Wells","sequence":"first","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, United 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