MYC deficiency impairs the development of effector/memory T lymphocytes

被引：11

作者：

Nozais, Mathis ^{[1
]}

Loosveld, Marie ^{[1
,2
]}

Pankaew, Saran ^{[1
]}

Grosjean, Clemence ^{[1
]}

Gentil, Noemie ^{[1
]}

Quessada, Julie ^{[1
]}

Nadel, Bertrand ^{[1
]}

Mionnet, Cyrille ^{[1
]}

Potier, Delphine ^{[1
]}

Payet-Bornet, Dominique ^{[1
]}

机构：

[1] Aix Marseille Univ, Ctr Immunol Marseille Luminy CIML, INSERM, CNRS, Parc Sci Luminy,Case 906, F-13288 Marseille 9, France

[2] Hop La Timone, AP HM, Lab Hematol, Marseille, France

来源：

ISCIENCE | 2021年 / 24卷 / 07期

基金：

欧盟地平线“2020”;

关键词：

CELL DEVELOPMENT; C-MYC; PTEN; CLASSIFICATION; PROLIFERATION; ACTIVATION; GENETICS; LEUKEMIA; PATHWAY; MICE;

D O I：

10.1016/j.isci.2021.102761

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

In the thymus, T cell progenitors differentiate in order to generate naive T lymphocytes which migrate in the periphery where they will fulfill their function in the adaptive immune response. During thymopoiesis, genomic alterations in thymocytes can promote leukemia development. Among recurrent alteration is PTEN inactivation, which is associated to MYC overexpression. Herein, we used conditional Pten and Myc knockout mouse models and single-cell RNA-sequencing approach, to investigate the impact of MYC loss on physio-pathological development of PTEN-proficient or PTEN-deficient T lymphocytes. First, our results confirm that MYC is mandatory for PTEN loss-mediated leukemogenesis, while it is not required for terminal steps of thymopoiesis. In contrast, we uncovered that Myc ablation in CD4(+)CD8(+) thymocytes disrupts T lymphocytes homeostasis in the spleen, notably by drastically reducing the number of MYC-deficient effector/memory T cells. Collectively, our data show that besides naive T cells proliferation, MYC is essential for effector/memory differentiation.

引用

页数：16

共 32 条

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