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Lgr5(+) 干细胞/祖细胞有助于肾脏发育过程中的肾单位形成。

Lgr5(+ve) stem/progenitor cells contribute to nephron formation during kidney development.

机构信息

Hubrecht Institute for Developmental Biology and Stem Cell Research/University Medical Centre Utrecht, Utrecht, The Netherlands.

出版信息

Cell Rep. 2012 Sep 27;2(3):540-52. doi: 10.1016/j.celrep.2012.08.018. Epub 2012 Sep 20.

Abstract

Multipotent stem cells and their lineage-restricted progeny drive nephron formation within the developing kidney. Here, we document expression of the adult stem cell marker Lgr5 in the developing kidney and assess the stem/progenitor identity of Lgr5(+ve) cells via in vivo lineage tracing. The appearance and localization of Lgr5(+ve) cells coincided with that of the S-shaped body around embryonic day 14. Lgr5 expression remained restricted to cell clusters within developing nephrons in the cortex until postnatal day 7, when expression was permanently silenced. In vivo lineage tracing identified Lgr5 as a marker of a stem/progenitor population within nascent nephrons dedicated to generating the thick ascending limb of Henle's loop and distal convoluted tubule. The Lgr5 surface marker and experimental models described here will be invaluable for deciphering the contribution of early nephron stem cells to developmental defects and for isolating human nephron progenitors as a prerequisite to evaluating their therapeutic potential.

摘要

多能干细胞及其谱系限制的后代在发育中的肾脏内驱动肾单位的形成。在这里,我们记录了成年干细胞标记物 Lgr5 在发育中的肾脏中的表达,并通过体内谱系追踪评估了 Lgr5(+ve)细胞的干细胞/祖细胞特性。Lgr5(+ve)细胞的出现和定位与胚胎第 14 天左右的 S 形体一致。Lgr5 的表达一直局限于皮质中发育中的肾单位内的细胞簇,直到出生后第 7 天,表达被永久沉默。体内谱系追踪将 Lgr5 鉴定为专门生成 Henle 袢升支粗段和远曲小管的新生肾单位内的干细胞/祖细胞群体的标志物。这里描述的 Lgr5 表面标志物和实验模型对于解析早期肾单位干细胞对发育缺陷的贡献以及分离人类肾单位祖细胞作为评估其治疗潜力的前提条件将是非常宝贵的。

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