Mutabaruka Marie S, Pata Monica, Vacher Jean
Institut de Recherches Cliniques de Montréal, 110 West Pins Avenue, Montréal, QC H2W 1R7, Canada.
Department of Medicine, Division of Experimental Medicine, McGill University, Montréal, QC H3A 1A3, Canada.
iScience. 2022 Mar 25;25(4):104160. doi: 10.1016/j.isci.2022.104160. eCollection 2022 Apr 15.
mutations cause the severe form of osteopetrosis with bone marrow deficiency in humans and mice, yet a role in T cell ontogeny remains to be determined. Herein, we show that thymi of the -null mice (gl/gl) from P8-to-P15 become markedly hypocellular with disturbed architecture. Analysis of gl/gl early T cell program determined a major decrease of 3-fold in bone marrow common lymphoid precursors (CLP), 35-fold in early thymic precursors (ETPs) and 100-fold in T cell double positive subpopulations. ablation in T cell double negative (DN) also appears to induce fast-paced differentiation kinetics with a transitory intermediate CD44CD25 subpopulation. Transgenic targeting expression from the gl/gl DN1 population partially rescued T cell subpopulations from ETP onwards and normalized the accelerated DN differentiation, indicating a cell-autonomous role for . Transcriptome of early DN1 population identified an crosstalk with a signaling axis. Our findings establish that is an essential regulator of T cell ontogeny.
突变在人类和小鼠中导致伴有骨髓缺陷的严重型骨质石化症，但其在T细胞个体发育中的作用仍有待确定。在此，我们表明，从P8到P15的-/-小鼠（gl/gl）的胸腺细胞明显减少，结构紊乱。对gl/gl早期T细胞程序的分析确定，骨髓共同淋巴前体（CLP）减少了3倍，早期胸腺前体（ETP）减少了35倍，T细胞双阳性亚群减少了100倍。在T细胞双阴性（DN）中敲除似乎也会诱导快速的分化动力学，出现一个短暂的中间CD44CD25亚群。从gl/gl DN1群体中转基因靶向表达部分挽救了从ETP开始的T细胞亚群，并使加速的DN分化正常化，表明具有细胞自主作用。早期DN1群体的转录组确定了与信号轴的串扰。我们的研究结果表明，是T细胞个体发育的重要调节因子。
