Cobas Monica, Wilson Anne, Ernst Bettina, Mancini Stéphane J C, MacDonald H Robson, Kemler Rolf, Radtke Freddy
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
J Exp Med. 2004 Jan 19;199(2):221-9. doi: 10.1084/jem.20031615. Epub 2004 Jan 12.
Beta-catenin-mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP-mediated inactivation of the beta-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is beta-catenin independent. In contrast to earlier reports, these data exclude an essential role for beta-catenin during hematopoiesis and lymphopoiesis.
β-连环蛋白介导的Wnt信号通路已被认为在免疫系统中造血干细胞的维持以及T细胞和B细胞的发育中起关键作用。出乎意料的是,我们在此报告,即使在竞争性混合嵌合体中,通过诱导性Cre-loxP介导的骨髓祖细胞中β-连环蛋白基因的失活也不会损害它们自我更新和重建所有造血谱系(髓系、红系和淋巴系)的能力。此外,胸腺细胞存活和外周T细胞的抗原诱导增殖均不依赖β-连环蛋白。与早期报告相反,这些数据排除了β-连环蛋白在造血和淋巴细胞生成过程中的重要作用。