A revised airway epithelial hierarchy includes CFTR-expressing ionocytes
The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary iono...
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| Format: | Article |
| Language: | English |
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Springer Nature
2020
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| Online Access: | https://hdl.handle.net/1721.1/125367 |
| _version_ | 1810997195271307264 |
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| author | Regev, Aviv |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Regev, Aviv |
| author_sort | Regev, Aviv |
| collection | MIT |
| description | The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term ‘hillocks’; and disease-relevant subsets of tuft and goblet cells. We developed ‘pulse-seq’, combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease. |
| first_indexed | 2024-09-23T14:25:12Z |
| format | Article |
| id | mit-1721.1/125367 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:25:12Z |
| publishDate | 2020 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | mit-1721.1/1253672022-09-29T09:23:33Z A revised airway epithelial hierarchy includes CFTR-expressing ionocytes Regev, Aviv Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term ‘hillocks’; and disease-relevant subsets of tuft and goblet cells. We developed ‘pulse-seq’, combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease. 2020-05-21T13:44:11Z 2020-05-21T13:44:11Z 2018-08 2020-01-28T15:24:22Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 https://hdl.handle.net/1721.1/125367 Montoro, Daniel T. et al. “A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.” Nature 560 (2018): 319-324 © 2018 The Author(s) en 10.1038/S41586-018-0393-7 Nature Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Springer Nature PMC |
| spellingShingle | Regev, Aviv A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title | A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title_full | A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title_fullStr | A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title_full_unstemmed | A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title_short | A revised airway epithelial hierarchy includes CFTR-expressing ionocytes |
| title_sort | revised airway epithelial hierarchy includes cftr expressing ionocytes |
| url | https://hdl.handle.net/1721.1/125367 |
| work_keys_str_mv | AT regevaviv arevisedairwayepithelialhierarchyincludescftrexpressingionocytes AT regevaviv revisedairwayepithelialhierarchyincludescftrexpressingionocytes |