Progenitor cells have clonogenicity, self-renewal, and multipotential capacity, and they can generate multiple types of cells during development. Evidence demonstrating the existence of such progenitor cells for renal distal segments is lacking.

To identify Aqp2⁺ progenitor (AP) cells, we performed in vivo lineage tracing using both constitutive (Aqp2Cre RFP/+) and Tamoxifen-inducible (Aqp2^ECE/+ RFP/+, Aqp2^ECE/+ Brainbow/+, and Aqp2^ECE/+ Brainbow/Brainbow) mouse models. Aqp2Cre RFP/+ mice were analyzed from E14.5 to adult stage. The inducible models were induced at P1 and examined at P3 and P42, respectively. Multiple segment- or cell-specific markers were used for high-resolution immunofluorescence confocal microscopy analyses to identify the cell types derived from Aqp2⁺ cells.

Both Aqp2Cre and Aqp2^ECE/+ faithfully indicate the activation of the endogenous Aqp2 promoter for lineage tracing. A subset of Aqp2⁺ cells behaves as potential AP. Aqp2Cre-based lineage tracing revealed that embryonic APs generate five types of cells, which form the late distal convoluted tubule (DCT2), connecting tubule segments 1 and 2 (CNT1 and CNT2, respectively), and collecting ducts (CDs). The α- and β-intercalated cells were apparently derived from embryonic AP in a stepwise manner. Aqp2^ECE/+-based lineage tracing identified cells coexpressing Aqp2 and V-ATPase subunits B1 and B2 as the potential AP. Neonate APs generate daughter cells either inheriting their property (self-renewal) or evolving into various DCT2, CNT, or CD cells (multipotentiality), forming single cell-derived multiple-cell clones (clonogenicity) during development.

Our study demonstrates that unique Aqp2⁺ B1B2⁺ cells are the potential APs to generate DCT2, CNT, CNT2, and CD segments.

祖细胞具有克隆形成、自我更新和多能能力，在发育过程中可以产生多种类型的细胞。缺乏证明肾远端节段存在此类祖细胞的证据。

为了识别 Aqp2 ⁺祖细胞 (AP) 细胞，我们使用组成型 ( Aqp2Cre RFP/+ ) 和他莫昔芬诱导型 ( Aqp2 ^ECE/+ RFP/+、Aqp2 ^ECE/+ Brainbow/+和Aqp2 ^{ECE/ +} Brainbow/Brainbow ) 鼠标模型。从 E14.5 到成年阶段对Aqp2Cre RFP/+小鼠进行了分析。可诱导模型在 P1 诱导，并分别在 P3 和 P42 进行检查。多个片段或细胞特异性标记用于高分辨率免疫荧光共聚焦显微镜分析，以鉴定源自 Aqp2 ⁺细胞的细胞类型。

Aqp2Cre和Aqp2 ^ECE/+都忠实地表明了用于谱系追踪的内源Aqp2启动子的激活。Aqp2 ⁺细胞的一个子集表现为潜在的 AP。基于Aqp2Cre的谱系追踪显示，胚胎 AP 产生五种类型的细胞，它们形成晚期远曲小管 (DCT2)，连接小管段 1 和 2（分别为 CNT1 和 CNT2）和集合管 (CD)。α - 和β - 插层细胞显然是逐步从胚胎 AP 衍生而来的。Aqp2 ^ECE/+基于谱系追踪确定共表达 Aqp2 和 V-ATPase 亚基 B1 和 B2 的细胞是潜在的 AP。新生儿 AP 生成子细胞，要么继承其特性（自我更新），要么进化成各种 DCT2、CNT 或 CD 细胞（多能性），在发育过程中形成单细胞衍生的多细胞克隆（克隆形成性）。

我们的研究表明，独特的 Aqp2 ⁺ B1B2 ⁺细胞是产生 DCT2、CNT、CNT2 和 CD 片段的潜在 AP。