The transcription factor Foxi1 promotes expression of V-ATPase and Gpr116 in M-1 cells.
The transcription factor Foxi1 promotes expression of V-ATPase and Gpr116 in M-1 cells.
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转录因子 Foxi1 促进 M-1 细胞中 V-ATPase 和 Gpr116 的表达。
DOI：
10.1152/ajprenal.00272.2022
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Zaidman,NathanA
中科院分区：
文献类型：
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作者：
Kui,Mackenzie;Pluznick,JenniferL;Zaidman,NathanA
每个肾单位片段的不同功能依赖于由其转录谱独特定义的专门细胞群的协调作用。在集合管中，有两个关键且不同的细胞群：主细胞和闰细胞。主细胞在水、Na+和K+的调节中发挥关键作用，而插细胞以其在酸碱稳态中的作用而闻名。目前，还没有体外系统能够概括集合管的异质性，这限制了遗传和生理现象的高通量和重复研究。在这里，我们证明转录因子 Foxi1 足以改变 M-1 细胞（一种小鼠皮质集合管细胞系）的转录特性。具体来说，Foxi1 的过表达会诱导插入细胞转录物的表达，包括 Gpr116、Atp6v1b1、Atp6v1g3、Atp6v0d2、Slc4a9 和 Slc26a4。这些数据表明 Foxi1 的过度表达使 M-1 细胞向非 A、非 B 型闰细胞表型分化，并可能为研究肾集合管的转录调控和生理功能提供一种新颖的体外工具。新的和值得注意的用转录因子 Foxi1 转染 M-1 细胞产生表达 V-ATPase 和 Gpr116 以及与肾集合管相关的其他基因的细胞 闰细胞。这种简单而新颖的体外系统可用于研究肾间质细胞的转录调控、细胞规格和分化等过程。
The diverse functions of each nephron segment rely on the coordinated action of specialized cell populations that are uniquely defined by their transcriptional profile. In the collecting duct, there are two critical and distinct cell populations: principal cells and intercalated cells. Principal cells play key roles in the regulation of water, Na+, and K+, whereas intercalated cells are best known for their role in acid-base homeostasis. Currently, there are no in vitro systems that recapitulate the heterogeneity of the collecting ducts, which limits high-throughput and replicate investigations of genetic and physiological phenomena. Here, we demonstrated that the transcription factor Foxi1 is sufficient to alter the transcriptional identity of M-1 cells, a murine cortical collecting duct cell line. Specifically, overexpression ofFoxi1induces the expression of intercalated cell transcripts includingGpr116,Atp6v1b1,Atp6v1g3,Atp6v0d2,Slc4a9, andSlc26a4. These data indicate that overexpression ofFoxi1differentiates M-1 cells toward a non-A, non-B type intercalated cell phenotype and may provide a novel in vitro tool to study transcriptional regulation and physiological function of the renal collecting duct.NEW & NOTEWORTHYTransfection of M-1 cells with the transcription factor Foxi1 generates cells that express V-ATPase and Gpr116 as well as other genes associated with renal intercalated cells. This straightforward and novel in vitro system could be used to study processes including transcriptional regulation and cell specification and differentiation in renal intercalated cells.