Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Eur J Immunol. 2013 May;43(5):1243-51. doi: 10.1002/eji.201242947. Epub 2013 Mar 21.
Leucine-rich repeat-containing G protein-coupled receptor (Lgr)5 is a marker for epithelial stem cells in the adult intestine of mice. Lgr5 transcripts have also been detected in the developing murine thymus, leading to speculation that Lgr5 is a marker for the long-sought stem cell of the thymus. To address the nature of the Lgr5-expressing thymic epithelial cells (TECs), we used Lgr5-GFP reporter mice. We show that epithelial cells expressing Lgr5 protein are present in the fetal thymus during a specific developmental window yet are no longer detectable at birth. To analyze the function of the Lgr5 protein during thymus development, we generated Lgr5(-/-) mice. These experiments unequivocally show that thymus development is not perturbed in the absence of Lgr5, that all TEC subsets develop in Lgr5(-/-) mice and that T cells are produced in the expected ratios. Finally, by using an inducible lineage tracing system to track the progeny of Lgr5(+) fetal TECs in vivo, we demonstrated that Lgr5(+) fetal TECs have no detectable progeny in the later fetal thymus. In sum, we show that presence of the Lgr5 protein is not a prerequisite for proper thymus organogenesis.
富含亮氨酸重复的 G 蛋白偶联受体 5（Lgr）5 是成年小鼠肠道上皮干细胞的标志物。Lgr5 转录本也在发育中的小鼠胸腺中被检测到，这导致人们推测 Lgr5 是胸腺中长期寻找的干细胞标志物。为了确定表达 Lgr5 的胸腺上皮细胞（TEC）的性质，我们使用了 Lgr5-GFP 报告小鼠。我们表明，在特定的发育窗口期间，表达 Lgr5 蛋白的上皮细胞存在于胎儿胸腺中，但在出生时不再检测到。为了分析 Lgr5 蛋白在胸腺发育过程中的功能，我们生成了 Lgr5(-/-) 小鼠。这些实验明确表明，在没有 Lgr5 的情况下，胸腺发育不会受到干扰，所有 TEC 亚群在 Lgr5(-/-) 小鼠中发育，并且 T 细胞以预期的比例产生。最后，通过使用诱导性谱系追踪系统在体内追踪 Lgr5(+) 胎儿 TEC 的后代，我们证明 Lgr5(+) 胎儿 TEC 在后期胎儿胸腺中没有可检测到的后代。总之，我们表明 Lgr5 蛋白的存在不是适当的胸腺器官发生的先决条件。
