differentiate into a mature nephron lineage in response to AKI to repair the proximal tubule. Background In response to severe kidney injury, the kidney epithelium displays remarkable regenerative capabilities driven by adaptable resident epithelial cells. To date, it has been widely considered that the adult kidney lacks multipotent stem cells; thus, the cellular lineages responsible for repairing proximal tubule damage are incompletely understood. Leucine-rich repeats and immunoglobulin-like domain protein 1–expressing cells (Lrig1+ cells) have been identified as a long-lived cell in various tissues that can induce epithelial tissue repair. Therefore, we hypothesized that Lrig1+ cells participate in kidney development and tissue regeneration. Methods We investigated the role of Lrig1+ cells in kidney injury using mouse models. The localization of Lrig1+ cells in the kidney was examined throughout mouse development. The function of Lrig1+ progeny cells in AKI repair was examined in vivo using a tamoxifen-inducible Lrig1-specific Cre recombinase-based lineage tracing in three different kidney injury mouse models. In addition, we conducted single-cell RNA sequencing to characterize the transcriptional signature of Lrig1+ cells and trace their progeny. Results Lrig1+ cells were present during kidney development and contributed to formation of the proximal tubule and collecting duct structures in mature mouse kidneys. In three-dimensional culture, single Lrig1+ cells demonstrated long-lasting propagation and differentiated into the proximal tubule and collecting duct lineages. These Lrig1+ proximal tubule cells highly expressed progenitor-like and quiescence-related genes, giving rise to a novel cluster of cells with regenerative potential in adult kidneys. Moreover, these long-lived Lrig1+ cells expanded and repaired damaged proximal tubule in response to three types of AKIs in mice. Conclusions These findings highlight the critical role of Lrig1+ cells in kidney regeneration....

中文翻译：

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Lrig1+ 细胞在肾脏修复中的再生作用


分化为成熟的肾单位谱系，响应 AKI 修复近端肾小管。背景 为了应对严重的肾损伤，肾上皮表现出由适应性强的常驻上皮细胞驱动的显着再生能力。迄今为止，人们普遍认为成人肾脏缺乏多能干细胞;因此，负责修复近端肾小管损伤的细胞谱系尚不完全清楚。富含亮氨酸的重复序列和表达免疫球蛋白样结构域蛋白 1 的细胞 （Lrig1+ 细胞） 已被确定为各种组织中的长寿命细胞，可诱导上皮组织修复。因此，我们假设 Lrig1 + 细胞参与肾脏发育和组织再生。方法 我们使用小鼠模型研究了 Lrig1 + 细胞在肾损伤中的作用。在整个小鼠发育过程中检查 Lrig1 + 细胞在肾脏中的定位。在三种不同的肾损伤小鼠模型中，使用他莫昔芬诱导的基于 Lrig1 特异性 Cre 重组酶的谱系追踪在体内检查 Lrig1 + 后代细胞在 AKI 修复中的功能。此外，我们进行了单细胞 RNA 测序以表征 Lrig1 + 细胞的转录特征并追踪其后代。结果 Lrig1 + 细胞存在于肾脏发育过程中，并有助于成熟小鼠肾脏近端肾小管和集合管结构的形成。在三维培养中，单个 Lrig1 + 细胞表现出持久的增殖并分化为近端肾小管和集合管谱系。这些 Lrig1+ 近端小管细胞高度表达祖细胞样和静止相关基因，从而在成人肾脏中产生具有再生潜力的新型细胞簇。 此外，这些长寿命的 Lrig1 + 细胞在小鼠的三种类型 AKI 下扩增和修复受损的近端小管。结论 这些发现突出了 Lrig1 + 细胞在肾脏再生中的关键作用。