| First Author | Chopp LB | Year | 2020 |
| Journal | Immunity | Volume | 53 |
| Issue | 6 | Pages | 1182-1201.e8 |
| PubMed ID | 33242395 | Mgi Jnum | J:305197 |
| Mgi Id | MGI:6706375 | Doi | 10.1016/j.immuni.2020.10.024 |
| Citation | Chopp LB, et al. (2020) An Integrated Epigenomic and Transcriptomic Map of Mouse and Human alphabeta T Cell Development. Immunity 53(6):1182-1201.e8 |
| abstractText | alphabeta lineage T cells, most of which are CD4(+) or CD8(+) and recognize MHC I- or MHC II-presented antigens, are essential for immune responses and develop from CD4(+)CD8(+) thymocytes. The absence of in vitro models and the heterogeneity of alphabeta thymocytes have hampered analyses of their intrathymic differentiation. Here, combining single-cell RNA and ATAC (chromatin accessibility) sequencing, we identified mouse and human alphabeta thymocyte developmental trajectories. We demonstrated asymmetric emergence of CD4(+) and CD8(+) lineages, matched differentiation programs of agonist-signaled cells to their MHC specificity, and identified correspondences between mouse and human transcriptomic and epigenomic patterns. Through computational analysis of single-cell data and binding sites for the CD4(+)-lineage transcription factor Thpok, we inferred transcriptional networks associated with CD4(+)- or CD8(+)-lineage differentiation, and with expression of Thpok or of the CD8(+)-lineage factor Runx3. Our findings provide insight into the mechanisms of CD4(+) and CD8(+) T cell differentiation and a foundation for mechanistic investigations of alphabeta T cell development. |
