Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia
Fate mapping using Cited1-CreERT2 mice demonstrates that the cap mesenchyme contains self-renewing progenitor cells and gives rise exclusively to nephronic epithelia
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DOI：
10.1016/j.ydbio.2007.10.014
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
de Caestecker, Mark
中科院分区：
文献类型：
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作者：
Boyle, Scott;Misfeldt, Andrew;de Caestecker, Mark
经典的组织重组和体外谱系追踪研究表明，浓缩的后肾间充质(MM)可在成人肾脏形成肾上皮。然而，这些研究没有区分帽状间充质和组成浓缩的MM的管前聚集体，也没有确定这些细胞是否具有自我更新的能力。为了解决这些问题，我们建立了Cited1-CreEe(T2)BAC转基因小鼠，它只在帽间充质中表达他莫昔芬调节的Cre重组酶。将这些小鼠与Rosa26R(LacZ)报告系杂交，并在注射他莫昔芬后的不同时间点评估LacZ阳性细胞的位置和细胞特性，进行命运定位。这些研究证实了先前对MM细胞命运的体外分析的预期结果，并提供了体内证据，证明帽状间充质对成人收集导管上皮没有贡献。此外，通过利用时间调控的Cre重组酶，这些研究表明，在肾脏发生的不同阶段出现的肾上皮在成人肾脏中有不同的空间分布，并首次证明了帽间充质中包括一群自我更新的上皮祖细胞。(C)2007 Elsevier Inc.保留所有权利。
Classic tissue recombination and in vitro lineage tracing studies suggest that condensed metanephric mesenchyme (MM) gives rise to nephronic epithelium of the adult kidney. However, these studies do not distinguish between cap mesenchyme and pre-tubular aggregates comprising the condensed MM, nor do they establish whether these cells have self-renewing capacity. To address these questions, we generated Cited1-CreEe(T2) BAC transgenic mice, which express tamoxifen-regulated Cre recombinase exclusively in the cap mesenchyme. Fate mapping was performed by crossing these mice with the Rosa26R(Lacz) reporter line and evaluating the location and cellular characteristics of LacZ positive cells at different time points following tamoxifen injection. These studies confirmed expected results from previous in vitro analysis of MM cell fate, and provide in vivo evidence that the cap mesenchyme does not contribute to collecting duct epithelium in the adult. Furthermore, by exploiting the temporally regulated Cre recombinase, these studies show that nephronic epithelium arising at different stages of nephrogenesis has distinct spatial distribution in the adult kidney, and demonstrate for the first time that the cap mesenchyme includes a population of self-renewing epithelial progenitor cells. (c) 2007 Elsevier Inc. All rights reserved.