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Single cell RNA-seq mapping of nasal and tracheobronchial airways in human healthy volunteers.

ABSTRACT: We have explored cellular heterogeneity of human airways in 10 healthy volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree, either by forceps (46,791 cells), or brush biopsies (31,178 cells). Use of cold-active proteases allowed dissociation of a high percentage of epithelial cells (89.1%, 15 distinct surface cell types and 2 glandular cell types), but also immune (6.2%, 7 cell types) and stromal (4.7%, 4 cell types) cells. Raw data has been submitted to EGA web portal under accession number EGAS00001004082 (https://ega-archive.org/studies/EGAS00001004082).

ORGANISM(S): Homo sapiens

PROVIDER: GSE143868 | GEO | 2021/01/11

REPOSITORIES: GEO

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79ea812b-5f07-48bf-9367-b51b85493b12 - samples

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Single cell RNA-seq mapping of nasal and tracheobronchial airways in human healthy volunteers

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Project description:Purpose: Tracheal epithelial brush cells are rare chemosensory cells defined by their expression of elements of the bitter taste transduction system, and known to activate the cholinergic nervous system in the murine lung. Similar chemosensory cells in the intestine can generate lipid mediators and pro-inflammatory cytokines but whether brush cell can contribute to airway inflammation is unknown. Furthermore, despite the advances in understanding chemosensory cell effector functions, the receptors that mediate chemosensory cell activation and expansion beyond taste receptors in any compartment remain largely unknown. Methods: In this study, we isolated tracheal brush cells by FACS from naïve ChATBAC-eGFP mice with knockin of eGFP within a BAC spanning the acetylcholine transferase locus, marking brush cells in the epithelium and performed transcriptome profiling using low input RNA sequencing. We compared tracheal brush cells to EpCAM+ epithelial cells and CD45+ hematopoetic cells in naive mice. Results: When compared to EpCAM+ EpCs and to CD45+ cells in the airway, principal component analysis demonstrated that brush cells grouped quite distinctly. This brush cell distinction relative to EpCAM+ cells, was further reflected in the striking number of highly differentially expressed genes. This included 1305 genes expressed at 4-fold or higher levels in EpCAM+eGFP+ cells (brush cells), of which 418 genes were expressed at 32-fold or higher levels in brush cells. Conclusions: Our study represents the first detailed analysis of the transcriptome of tracheal brush cells and identifies a unique set of genes that are primarily expressed in brush cells including the bitter taste transduction system, synthenic machinery for several pro-inflammatory lipid mediators and HoxA2 transciptional factors.

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RNA-Seq of polyA mRNA from plasma cells of tonsil from healthy individuals in the BLUEPRINT epigenome project

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