Wafaa Mahmoud, Alexander Perniss, Krupali Poharkar, Maryam Keshavarz, Ulrich Gärtner, Johannes Oberwinkler, Burkhard Schütz, Thomas Worzfeld, Stefan Offermanns, Wolfgang Kummer
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引用次数: 0
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.
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.