Department of Immunology, Tokai University School of Medicine, Isehara, Japan.
Institute of Medical Sciences, Tokai University, Isehara, Japan.
Elife. 2021 Aug 12;10:e68227. doi: 10.7554/eLife.68227.
Notch signaling primarily determines T-cell fate. However, the molecular mechanisms underlying the maintenance of T-lineage potential in pre-thymic progenitors remain unclear. Here, we established two murine -deficient pro-B cell lines, with and without T-lineage potential. The latter expressed lower levels of ; their potential was restored via ectopic expression of . Conversely, the CRISPR/Cas9-mediated deletion of resulted in the loss of the T-lineage potential. Introduction of rescued massive cell death of Notch-stimulated pro-B cells without efficient LMO2-driven expression but was not sufficient to retain their T-lineage potential. Pro-B cells without T-lineage potential failed to activate due to DNA methylation; transduction restored this capacity. Moreover, direct binding of LMO2 to the and loci was observed. Altogether, our results highlight LMO2 as a crucial player in the survival and maintenance of T-lineage potential in T-cell progenitors via the regulation of the expression of and .
Notch 信号主要决定 T 细胞命运。然而，在前胸腺祖细胞中维持 T 细胞谱系潜能的分子机制仍不清楚。在这里，我们建立了两个具有和不具有 T 细胞谱系潜能的小鼠 - 缺陷的前 B 细胞系。后者表达较低水平的 ; 它们的潜能通过异位表达 得到恢复。相反，CRISPR/Cas9 介导的 缺失导致 T 细胞谱系潜能丧失。引入 挽救了 Notch 刺激的前 B 细胞的大量细胞死亡，但没有有效驱动 的表达，也不足以保留其 T 细胞谱系潜能。没有 T 细胞谱系潜能的前 B 细胞由于 DNA 甲基化而不能激活 ； 转导恢复了这种能力。此外，还观察到 LMO2 与 和 基因座的直接结合。总之，我们的研究结果强调了 LMO2 作为一个关键的调控因子，通过调节 的表达，在 T 细胞祖细胞中维持 T 细胞谱系潜能的生存和维持方面发挥作用。
