Adult progenitor cells presumably demonstrate clonogenicity, self-renewal, and multipotentiality, and can regenerate cells under various conditions. Definitive evidence demonstrating the existence of such progenitor cells in adult mammalian kidneys is lacking.

We performed in vivo lineage tracing and thymidine analogue labeling using adult tamoxifen-inducible (Aqp2^ECE/+ RFP/+, Aqp2^ECE/+ Brainbow/+, and Aqp2^ECE/+ Brainbow/Brainbow) and WT mice. The tamoxifen-inducible mice were analyzed between 1 and 300 days postinduction. Alternatively, WT and tamoxifen-induced mice were subjected to unilateral ureteral obstruction and thymidine analogue labeling and analyzed 2–14 days post-surgery. Multiple cell-specific markers were used for high-resolution immunofluorescence confocal microscopy to identify the cell types derived from Aqp2⁺ cells.

Like their embryonic counterparts, adult cells expressing Aqp2 and V-ATPase subunits B1 and B2 (Aqp2⁺ B1B2⁺) are the potential Aqp2⁺ progenitor cells (APs). Adult APs rarely divide to generate daughter cells, either maintaining the property of the AP (self-renewal) or differentiating into DCT2/CNT/CD cells (multipotentiality), forming single cell–derived, multiple-cell clones (clonogenicity) during tissue maintenance. APs selectively and continuously regenerate DCT2/CNT/CD cells in response to injury resulting from ureteral ligation. AP proliferation demonstrated direct correlation with Notch activation and was inversely correlated with development of kidney fibrosis. Derivation of both intercalated and DCT2 cells was found to be cell division–dependent and –independent, most likely through AP differentiation which requires cell division and through direct conversion of APs and/or regular principal cells without cell division, respectively.

Our study demonstrates that Aqp2⁺ B1B2⁺ cells behave as adult APs to maintain and repair DCT2/CNT1/CNT2/CD segments.

成体祖细胞可能表现出克隆性、自我更新和多潜能，并且可以在各种条件下再生细胞。缺乏确凿的证据证明成年哺乳动物肾脏中存在此类祖细胞。

我们使用成年他莫昔芬诱导型（Aqp2 ^ECE/+ RFP/+、Aqp2 ^ECE/+ Brainbow/+和Aqp2 ^ECE/+ Brainbow/Brainbow）和 WT 小鼠进行体内谱系追踪和胸苷类似物标记。在诱导后 1 至 300 天之间对他莫昔芬诱导型小鼠进行分析。或者，对 WT 和他莫昔芬诱导的小鼠进行单侧输尿管梗阻和胸苷类似物标记，并在术后 2-14 天进行分析。使用多种细胞特异性标记物进行高分辨率免疫荧光共聚焦显微镜来鉴定源自 Aqp2 ⁺细胞的细胞类型。

与胚胎细胞一样，表达 Aqp2 和 V-ATPase 亚基 B1 和 B2 (Aqp2 ⁺ B1B2 ⁺ ) 的成体细胞是潜在的 Aqp2 ⁺祖细胞（AP）。成体 AP 很少分裂产生子细胞，要么保持 AP 的特性（自我更新），要么分化为 DCT2/CNT/CD 细胞（多能性），在组织维持过程中形成单细胞衍生的多细胞克隆（克隆性） 。AP 选择性地持续再生 DCT2/CNT/CD 细胞，以响应输尿管结扎造成的损伤。AP 增殖与 Notch 激活直接相关，与肾纤维化的发展呈负相关。发现插层细胞和 DCT2 细胞的衍生是细胞分裂依赖性和独立性的，最有可能分别通过需要细胞分裂的 AP 分化和通过 AP 和/或常规主细胞的直接转化而无需细胞分裂。

我们的研究表明，Aqp2 ⁺ B1B2 ⁺细胞的行为与成年 AP 一样，可以维持和修复 DCT2/CNT1/CNT2/CD 片段。