| Autor: |
Marie S. Mutabaruka, Monica Pata, Jean Vacher |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 25, Iss 4, Pp 104160- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2022.104160 |
| Popis: |
Summary: Ostm1 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 Ostm1-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. Ostm1 ablation in T cell double negative (DN) also appears to induce fast-paced differentiation kinetics with a transitory intermediate CD44+CD25int subpopulation. Transgenic targeting Ostm1 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 Ostm1. Transcriptome of early DN1 population identified an Ostm1 crosstalk with a Foxo1-Klf2-S1pr1-Gnai1-Rac1 signaling axis. Our findings establish that Ostm1 is an essential regulator of T cell ontogeny. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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