β-catenin and γ-catenin are dispensable for T lymphocytes and AML leukemic stem cells

• Published in: eLife Vol. 9
• Main Authors: Zhao, Xin, Shao, Peng, Gai, Kexin, Li, Fengyin, Shan, Qiang, Xue, Hai-Hui
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications, Ltd 21.08.2020; eLife Sciences Publications Ltd
• Subjects: acute myeloid leukemia; beta Catenin - genetics; beta Catenin - metabolism; beta-catenin; gamma Catenin - genetics; gamma Catenin - metabolism; gamma-catenin; Immunology and Inflammation; Leukemia - metabolism; leukemic stem cells; Neoplastic Stem Cells - physiology; Short Report; Stem Cells and Regenerative Medicine; T lymphocytes; T-Lymphocytes - metabolism; Tcf/Lef; T lymphocytes; beta-catenin; mouse; stem cells; acute myeloid leukemia; inflammation; leukemic stem cells; regenerative medicine; Tcf/Lef; immunology; gamma-catenin
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.55360

The β-catenin transcriptional coregulator is involved in various biological and pathological processes; however, its requirements in hematopoietic cells remain controversial. We re-targeted the gene locus to generate a true β-catenin-null mutant mouse strain. Ablation of β-catenin alone, or in combination with its homologue γ-catenin, did not affect thymocyte maturation, survival or proliferation. Deficiency in β/γ-catenin did not detectably affect differentiation of CD4 T follicular helper cells or that of effector and memory CD8 cytotoxic cells in response to acute viral infection. In an MLL-AF9 AML mouse model, genetic deletion of β-catenin, or even all four Tcf/Lef family transcription factors that interact with β-catenin, did not affect AML onset in primary recipients, or the ability of leukemic stem cells (LSCs) in propagating AML in secondary recipients. Our data thus clarify on a long-standing controversy and indicate that β-catenin is dispensable for T cells and AML LSCs.