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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010627 | PMC |
| http://dx.doi.org/10.1016/j.isci.2022.104160 | DOI Listing |
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