Lgr5+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development
Lgr5+ve Stem/Progenitor Cells Contribute to Nephron Formation during Kidney Development
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DOI：
10.1016/j.celrep.2012.08.018
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发表时间：
2012-09-01
期刊：
影响因子：
8.8
通讯作者：
Clevers, Hans
中科院分区：
文献类型：
--
作者：
Barker, Nick;Rookmaaker, Maarten B.;Clevers, Hans
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形成。在这里，我们通过体内谱系跟踪记录了发育中的肾脏中成年干细胞标记LGR5 LGR5的表达，并评估LGR5（+VE）细胞的茎/祖细胞身份。 LGR5（+VE）细胞的外观和定位与胚胎第14天左右的S形体的外观相吻合。LGR5表达一直限于在皮质中发育的肾单位中的细胞簇，直到第7天，当时表达是永久沉默的。体内谱系跟踪将LGR5鉴定为新生肾中茎/祖先种群的标记，该标志是致力于产生Henle环和远端曲折小管的较厚上升肢。 LGR5表面标记和此处描述的实验模型对于破译早期肾单位干细胞对发育缺陷的贡献和分离人肾祖细胞的贡献是无价的，这是评估其治疗潜力的先决条件。
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.