基因谱系示踪揭示小鼠Tbx18^+肾脏间质祖细胞分化为输尿管平滑肌

Genetic Fate Mapping Reveals the Differentiation of Tbx18^+ Mouse Kidney Mesenchyme Progenitors into Ureteral Smooth Muscle

本文旨在研究Tbx18+肾脏间质祖细胞分化为输尿管平滑肌细胞的命运及转录因子Tbx18在小鼠输尿管平滑肌发育形成中起到的作用.实验建立Tbx18:Cre/R26REYFP和Tbx18:Cre/R26RLacZ两种谱系示踪系统和Tbx18:Cre/Cre敲除模型.该示踪模型通过cre重组酶的表达能有效地示踪Tbx18+肾脏间质祖细胞在泌尿系统的发育命运.通过免疫荧光染色和X-gal染色,同时发现Tbx18+肾脏间质祖细胞可分化为输尿管平滑肌细胞,但不分化为输尿管移行上皮细胞.在Tbx18:Cre/Cre基因突变模型中,泌尿系统出现明显的肾积水和输尿管积水,肾盏、肾盂扩张,输尿管明显缩短和扩张.实验结果揭示,Tbx18+肾脏间质祖细胞可以分化为输尿管平滑肌细胞,且转录因子Tbx18在哺乳动物输尿管平滑肌的发育中起到重要的作用.

Here we elucidate the potential of Tbx18 ＋ smooth muscle and the function of T-box transcription mesenchyme progenitors differentiation into ＇ureteral factor Tbx18 in the forming of smooth muscle in the ureter. We present phenotypic characterization of mouse models of genetic fate-mapping systems Tbx18： Cre/R26REYFP and Tbx18： Cre/R26RLacZ double heterozygous, founded by Cre-loxP system. Meanwhile, Tbx18 ：Cre/Cre mutant mice model was also adopted. The double-heterozygous mice through monitoring the expression of Cre effectively revealed Tbx18-1ineage-traced cells in the ureter. We found that Tbx18 ＋ mesenchyme progenitors give rise to most smooth muscle cells in the ureter but not ureteric epithelium ceils in vivo by the immunoflourescence and X-gal staining of the tissue. In the model of Tbx18：Cre/Cre mutant mice, urogenital systerms displayed a prominent hydronephrosis and hydroureter phenotype with a dilation of the pelvicaliceal space and the mutant ureters of sever length reduction. We reveal that Tbx18 ＋ mesenchyme progenitors differentiate into ureteral muscle and Tbx18 plays a key role in the differentiation fate of ureteral smooth muscle cells.