| First Author | Paiva RA | Year | 2021 |
| Journal | Cell Rep | Volume | 35 |
| Issue | 2 | Pages | 108967 |
| PubMed ID | 33852867 | Mgi Jnum | J:353215 |
| Mgi Id | MGI:6716782 | Doi | 10.1016/j.celrep.2021.108967 |
| Citation | Paiva RA, et al. (2021) Self-renewal of double-negative 3 early thymocytes enables thymus autonomy but compromises the beta-selection checkpoint. Cell Rep 35(2):108967 |
| abstractText | T lymphocyte differentiation in the steady state is characterized by high cellular turnover whereby thymocytes do not self-renew. However, if deprived of competent progenitors, the thymus can temporarily maintain thymopoiesis autonomously. This bears a heavy cost, because prolongation of thymus autonomy causes leukemia. Here, we show that, at an early stage, thymus autonomy relies on double-negative 3 early (DN3e) thymocytes that acquire stem-cell-like properties. Following competent progenitor deprivation, DN3e thymocytes become long lived, are required for thymus autonomy, differentiate in vivo, and include DNA-label-retaining cells. At the single-cell level, the transcriptional programs of thymopoiesis in autonomy and the steady state are similar. However, a new cell population emerges in autonomy that expresses an aberrant Notch target gene signature and bypasses the beta-selection checkpoint. In summary, DN3e thymocytes have the potential to self-renew and differentiate in vivo if cell competition is impaired, but this generates atypical cells, probably the precursors of leukemia. |
