Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ciência, Calouste Gulbenkian Foundation, Oeiras, 2780-156, Portugal.
Lymphocyte Development and Leukemogenesis Laboratory, Instituto Gulbenkian de Ciência, Calouste Gulbenkian Foundation, Oeiras, 2780-156, Portugal.
Dev Biol. 2021 Jul;475:1-9. doi: 10.1016/j.ydbio.2021.02.013. Epub 2021 Feb 27.
Cell competition contributes to optimal organ function by promoting tissue homogeneity. In the hematopoietic system, cell competition has been described in two distinct cell populations: in hematopoietic stem cells, and in differentiating T lymphocytes, or thymocytes. In hematopoietic stem cells, cell competition was studied in the context of mild irradiation, whereby the levels of p53 determined the outcome of the cellular interactions and the cells with lower p53 were in advantage. In the thymus, cell competition was addressed in thymus transplantation experiments, and found to be a homeostatic process that contributes to thymus turnover. Cell competition in the thymus depends on the capacity of T lymphocyte precursors to respond to interleukin 7 (IL-7). Failed cell competition permitted thymocyte self-renewal and autonomous thymopoiesis for several weeks, that culminated with leukemia onset. Beyond the work addressing cell competition in these cells, we discuss current hypotheses and observations that could be explained by cell competition. These include the clonal dynamics of hematopoietic stem cells in the ageing organism and initiation of leukemia.
细胞竞争通过促进组织均一性来促进最佳器官功能。在造血系统中,细胞竞争已在两种不同的细胞群体中被描述:造血干细胞和分化的 T 淋巴细胞或胸腺细胞。在造血干细胞中,细胞竞争是在轻度辐射的背景下研究的,其中 p53 的水平决定了细胞相互作用的结果,并且 p53 水平较低的细胞处于优势地位。在胸腺中,通过胸腺移植实验解决了细胞竞争问题,并发现它是一种有助于胸腺更新的动态平衡过程。胸腺中的细胞竞争取决于 T 淋巴细胞前体对白细胞介素 7(IL-7)的反应能力。失败的细胞竞争允许胸腺细胞自我更新和自主胸腺生成数周,最终导致白血病的发生。除了针对这些细胞中的细胞竞争的工作之外,我们还讨论了当前的假设和观察结果,这些结果可以通过细胞竞争来解释。其中包括衰老机体中造血干细胞的克隆动力学和白血病的起始。