Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, 3584 CT Utrecht, The Netherlands.
Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.
Proc Natl Acad Sci U S A. 2017 Dec 26;114(52):E11190-E11198. doi: 10.1073/pnas.1714145115. Epub 2017 Dec 13.
During kidney development, progressively committed progenitor cells give rise to the distinct segments of the nephron, the functional unit of the kidney. Similar segment-committed progenitor cells are thought to be involved in the homeostasis of adult kidney. However, markers for most segment-committed progenitor cells remain to be identified. Here, we evaluate as a segment-committed nephron progenitor cell marker. Troy is expressed in the ureteric bud during embryonic development. During postnatal nephrogenesis, Troy cells are present in the cortex and papilla and display an immature tubular phenotype. Tracing of Troy cells during nephrogenesis demonstrates that Troy cells clonally give rise to tubular structures that persist for up to 2 y after induction. Troy cells have a 40-fold higher capacity than Troy cells to form organoids, which is considered a stem cell property in vitro. In the adult kidney, Troy cells are present in the papilla and these cells continue to contribute to collecting duct formation during homeostasis. The number of Troy-derived cells increases after folic acid-induced injury. Our data show that Troy marks a renal stem/progenitor cell population in the developing kidney that in adult kidney contributes to homeostasis, predominantly of the collecting duct, and regeneration.
在肾脏发育过程中，逐渐定型的祖细胞产生了肾脏的功能单位——肾单位的不同节段。人们认为类似的节段定型祖细胞参与了成人肾脏的稳态维持。然而，大多数节段定型祖细胞的标志物仍有待确定。在这里，我们评估作为节段定型的肾祖细胞标志物。Troy 在胚胎发育过程中表达于输尿管芽中。在出生后肾发生期间，Troy 细胞存在于皮质和乳头中，并显示出不成熟的管状表型。在肾发生过程中对 Troy 细胞进行示踪表明，Troy 细胞克隆性地产生持续存在长达 2 年的管状结构。与 Troy 细胞相比，Troy 细胞形成类器官的能力高出 40 倍，这在体外被认为是干细胞的特性。在成年肾脏中，Troy 细胞存在于乳头上，这些细胞在稳态过程中继续有助于集合管的形成。叶酸诱导损伤后，Troy 衍生细胞的数量增加。我们的数据表明，Troy 标记了发育肾脏中的肾干细胞/祖细胞群体，在成年肾脏中，该群体主要参与了集合管的稳态维持、再生。
