Differential expression of villin and advillin by neuroendocrine and tuft cells in the murine lower airways.

IF 2.9 3区 生物学 Q3 CELL BIOLOGY
Cell and Tissue Research Pub Date : 2025-10-01 Epub Date: 2025-09-01 DOI:10.1007/s00441-025-04003-y
Wafaa Mahmoud, Alexander Perniss, Krupali Poharkar, Maryam Keshavarz, Ulrich Gärtner, Johannes Oberwinkler, Burkhard Schütz, Thomas Worzfeld, Stefan Offermanns, Wolfgang Kummer
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Abstract

Previous studies identified a rare cell type in the mouse tracheal epithelium with immunoreactivity to the microvillus protein villin (Vil1), which persisted in mice lacking tuft cells due to deletion of the transcription factor Pou2f3. This study aimed to clarify the identity of this ill-defined cell type. Ultrastructurally, all cells with tightly packed microvilli observed in the tracheal epithelium of Pou2f3-/--mice contained basally located dense core vesicles, a characteristic feature of neuroendocrine cells (NEC). Accordingly, immunofluorescence double-labeling utilizing NEC markers revealed villin-labeling in two thirds of NEC in the trachea, a reporter mouse strain showed Cre recombinase activity driven by the Vil1 promoter in a subpopulation of tracheal NEC, and analysis of single cell RNA sequencing data revealed Vil1-mRNA expression by tracheal NEC. Notably, only a minimal fraction (≈1%) of bronchopulmonary NEC (solitary and clustered in neuroepithelial bodies) displayed villin-immunoreactivity, despite nearly half of them having a history of Vil1 promoter activity. Microvilli of tuft cells differed ultrastructurally from those of NEC, and the majority of tuft cells were immunoreactive to advillin (Avil), showed Avil promoter activity as indicated by a reporter mouse strain, and expressed Avil-mRNA in the sequencing data set. This study uncovers villin-expressing cells in the lower airways as a cell population hidden among NEC. Advillin, not villin, is identified as a marker for airway tuft cells. This should be considered in interpreting findings based on the use of villin as a marker or Cre-driver when investigating rare cells in the murine airways.

绒毛蛋白和肾上腺素在小鼠下气道神经内分泌和簇状细胞中的差异表达。
先前的研究在小鼠气管上皮中发现了一种罕见的细胞类型,它对微绒毛蛋白绒毛蛋白(Vil1)具有免疫反应性,由于转录因子Pou2f3的缺失,这种细胞类型在缺乏簇状细胞的小鼠中持续存在。这项研究旨在澄清这种不明确的细胞类型的身份。在超微结构上,在Pou2f3-/-小鼠气管上皮中观察到的所有微绒毛紧密堆积的细胞都含有位于基部的致密核心囊泡,这是神经内分泌细胞(NEC)的特征。因此,利用NEC标记的免疫荧光双标记显示,三分之二的气管NEC中有绒毛蛋白标记,报告鼠品系在气管NEC亚群中显示由Vil1启动子驱动的Cre重组酶活性,单细胞RNA测序数据分析显示气管NEC中有Vil1- mrna表达。值得注意的是,只有一小部分(≈1%)的支气管肺NEC(孤立的和聚集在神经上皮小体中)表现出绒毛蛋白免疫反应性,尽管其中近一半具有Vil1启动子活性的历史。tuft细胞的微绒毛在超微结构上与NEC细胞不同,大多数tuft细胞对阿维林(Avil)具有免疫反应,报告小鼠菌株显示Avil启动子活性,并在测序数据集中表达Avil- mrna。本研究揭示了下气道中绒毛蛋白表达细胞作为一个隐藏在NEC中的细胞群。Advillin,而不是绒毛蛋白,被认为是气道簇状细胞的标记物。当研究小鼠气道中的稀有细胞时,在解释基于绒毛蛋白作为标记物或cre驱动物的发现时,应考虑到这一点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell and Tissue Research
Cell and Tissue Research 生物-细胞生物学
CiteScore
7.00
自引率
2.80%
发文量
142
审稿时长
1 months
期刊介绍: The journal publishes regular articles and reviews in the areas of molecular, cell, and supracellular biology. In particular, the journal intends to provide a forum for publishing data that analyze the supracellular, integrative actions of gene products and their impact on the formation of tissue structure and function. Submission of papers with an emphasis on structure-function relationships as revealed by recombinant molecular technologies is especially encouraged. Areas of research with a long-standing tradition of publishing in Cell & Tissue Research include: - neurobiology - neuroendocrinology - endocrinology - reproductive biology - skeletal and immune systems - development - stem cells - muscle biology.
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