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转录因子使小鼠肾集合管中的细胞形成特定模式。

Transcription factor patterns cells in the mouse kidney collecting ducts.

作者信息

Werth Max, Schmidt-Ott Kai M, Leete Thomas, Qiu Andong, Hinze Christian, Viltard Melanie, Paragas Neal, Shawber Carrie J, Yu Wenqiang, Lee Peter, Chen Xia, Sarkar Abby, Mu Weiyi, Rittenberg Alexander, Lin Chyuan-Sheng, Kitajewski Jan, Al-Awqati Qais, Barasch Jonathan

机构信息

Columbia University, New York, United States.

Max Delbruck Center for Molecular Medicine, Berlin, Germany.

出版信息

Elife. 2017 Jun 3;6:e24265. doi: 10.7554/eLife.24265.

DOI:10.7554/eLife.24265
PMID:28577314
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5484618/
Abstract

Although most nephron segments contain one type of epithelial cell, the collecting ducts consists of at least two: intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively. In adult kidneys, these cells are organized in rosettes suggesting functional interactions. Genetic studies in mouse revealed that transcription factor coordinates IC and PC development. induces the expression of IC specific genes, including specific H-ATPase subunits and in turn, initiates Notch signaling in PCs but inhibits Notch signaling in ICs. inactivation deletes ICs, whereas inactivation results in the forfeiture of discrete IC and PC identities. Thus, is a critical regulator of IC-PC patterning, acting cell-autonomously in ICs, and non-cell-autonomously in PCs. As a result, regulates the diversification of cell types which is the central characteristic of 'salt and pepper' epithelia and distinguishes the collecting duct from all other nephron segments.

摘要

尽管大多数肾单位节段只包含一种上皮细胞类型，但集合管至少由两种细胞组成：闰细胞（IC）和主细胞（PC），它们分别调节酸碱平衡和盐水平衡。在成年肾脏中，这些细胞呈玫瑰花结状排列，提示存在功能相互作用。对小鼠的遗传学研究表明，转录因子协调闰细胞和主细胞的发育。它诱导闰细胞特异性基因的表达，包括特定的H-ATP酶亚基，进而在主细胞中启动Notch信号通路，但在闰细胞中抑制Notch信号通路。该基因失活会导致闰细胞缺失，而另一个基因失活则会导致离散的闰细胞和主细胞身份丧失。因此，该基因是闰细胞-主细胞模式形成的关键调节因子，在闰细胞中自主发挥作用，在主细胞中非自主发挥作用。结果，它调节细胞类型的多样化，这是“椒盐”上皮的核心特征，也是集合管与所有其他肾单位节段的区别所在。

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