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发帖数: 1003 | 1 老的T细胞如果不被新生取代的话，容易生成tumor。
Cell competition is a tumour suppressor mechanism in the thymus
Cell competition is an emerging principle underlying selection for cellular
fitness during development and disease. Competition may be relevant for
cancer, but an experimental link between defects in competition and
tumorigenesis is elusive. In the thymus, T lymphocytes develop from
precursors that are constantly replaced by bone-marrow-derived progenitors.
Here we show that in mice this turnover is regulated by natural cell
competition between ‘young’ bone-marrow-derived and ‘old’ thymus-
resident progenitors that, although genetically identical, execute
differential gene expression programs. Disruption of cell competition leads
to progenitor self-renewal, upregulation of Hmga1, transformation, and T-
cell acute lymphoblastic leukaemia (T-ALL) resembling the human disease in
pathology, genomic lesions, leukaemia-associated transcripts, and activating
mutations in Notch1. Hence, cell competition is a tumour suppressor
mechanism in the thymus. Failure to select fit progenitors through cell
competition may explain leukaemia in X-linked severe combined immune
deficiency patients who showed thymus-autonomous T-cell development after
therapy with gene-corrected autologous progenitors. |
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