{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:22:35Z","timestamp":1790760155837,"version":"4.1.0"},"reference-count":58,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2,28]]},"abstract":"<jats:p>The respiratory tract is lined by a pseudo-stratified epithelium from the nose to terminal bronchioles. This first line of defense of the lung against external stress includes five main cell types: basal, suprabasal, club, goblet and multiciliated cells, as well as rare cells such as ionocytes, neuroendocrine and tuft\/brush cells. At homeostasis, this epithelium self-renews at low rate but is able of fast regeneration upon damage. Airway epithelial cell lineages during regeneration have been investigated in the mouse by genetic labeling, mainly after injuring the epithelium with noxious agents. From these approaches, basal cells have been identified as progenitors of club, goblet and multiciliated cells, but also of ionocytes and neuroendocrine cells. Single-cell RNA sequencing, coupled to lineage inference algorithms, has independently allowed the establishment of comprehensive pictures of cell lineage relationships in both mouse and human. In line with genetic tracing experiments in mouse trachea, studies using single-cell RNA sequencing (RNAseq) have shown that basal cells first differentiate into club cells, which in turn mature into goblet cells or differentiate into multiciliated cells. In the human airway epithelium, single-cell RNAseq has identified novel intermediate populations such as deuterosomal cells, \u2018hybrid\u2019 mucous-multiciliated cells and progenitors of rare cells. Novel differentiation dynamics, such as a transition from goblet to multiciliated cells have also been discovered. The future of cell lineage relationships in the respiratory tract now resides in the combination of genetic labeling approaches with single-cell RNAseq to establish, in a definitive manner, the hallmarks of cellular lineages in normal and pathological situations.<\/jats:p>","DOI":"10.1042\/bst20191010","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T12:28:53Z","timestamp":1578659333000},"page":"327-336","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Using single-cell RNA sequencing to unravel cell lineage relationships in the respiratory tract"],"prefix":"10.1042","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6747-7928","authenticated-orcid":false,"given":"L.E.","family":"Zaragosi","sequence":"first","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CNRS, IPMC, Sophia-Antipolis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Deprez","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CNRS, IPMC, Sophia-Antipolis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Barbry","sequence":"additional","affiliation":[{"name":"Universit\u00e9 C\u00f4te d'Azur, CNRS, IPMC, Sophia-Antipolis, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2020,1,10]]},"reference":[{"key":"2021111915574510000_BST-2019-1010C1","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.pharmthera.2013.07.008","article-title":"Bronchial epithelium as a target for innovative treatments in asthma","volume":"140","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"2021111915574510000_BST-2019-1010C2","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1038\/nm.3642","article-title":"Lung regeneration: mechanisms, applications and emerging stem cell populations","volume":"20","year":"2014","journal-title":"Nat. Med."},{"key":"2021111915574510000_BST-2019-1010C3","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/s41586-018-0393-7","article-title":"A revised airway epithelial hierarchy includes CFTR-expressing ionocytes","volume":"560","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C4","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1172\/JCI27690","article-title":"Mucus in chronic airway diseases: sorting out the sticky details","volume":"116","year":"2006","journal-title":"J. Clin. Invest."},{"key":"2021111915574510000_BST-2019-1010C5","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/01913120290104566","article-title":"The ultrastructure of nasal mucosa in children with asthma","volume":"26","year":"2002","journal-title":"Ultrastruct. Pathol."},{"key":"2021111915574510000_BST-2019-1010C6","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1165\/rcmb.2009-0151TR","article-title":"Advances in mucous cell metaplasia: a plug for mucus as a therapeutic focus in chronic airway disease","volume":"42","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021111915574510000_BST-2019-1010C7","doi-asserted-by":"publisher","first-page":"12771","DOI":"10.1073\/pnas.0906850106","article-title":"Basal cells as stem cells of the mouse trachea and human airway epithelium","volume":"106","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111915574510000_BST-2019-1010C8","doi-asserted-by":"publisher","first-page":"362","DOI":"10.2353\/ajpath.2010.090870","article-title":"Tracheal basal cells: a facultative progenitor cell pool","volume":"177","year":"2010","journal-title":"Am. J. Pathol."},{"key":"2021111915574510000_BST-2019-1010C9","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.stem.2014.07.012","article-title":"Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function","volume":"15","year":"2014","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C10","doi-asserted-by":"publisher","first-page":"2000","DOI":"10.1164\/ajrccm.157.6.9707011","article-title":"Number and proliferation of basal and parabasal cells in normal human airway epithelium","volume":"157","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021111915574510000_BST-2019-1010C11","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.stem.2015.01.002","article-title":"Injury induces direct lineage segregation of functionally distinct airway basal stem\/progenitor cell subpopulations","volume":"16","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C12","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.celrep.2015.06.011","article-title":"Clonal dynamics reveal two distinct populations of basal cells in slow-turnover airway epithelium","volume":"12","year":"2015","journal-title":"Cell Rep."},{"key":"2021111915574510000_BST-2019-1010C13","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1164\/ajrccm.159.5.9806044","article-title":"Number and proliferation of clara cells in normal human airway epithelium","volume":"159","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021111915574510000_BST-2019-1010C14","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.4049\/jimmunol.171.2.1051","article-title":"Clara cell secretory protein modulates lung inflammatory and immune responses to respiratory syncytial virus infection","volume":"171","year":"2003","journal-title":"J. Immunol."},{"key":"2021111915574510000_BST-2019-1010C15","first-page":"316","article-title":"Xenobiotic metabolism in Clara cells and alveolar type II cells isolated from lungs of rats treated with beta-naphthoflavone","volume":"225","year":"1983","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"2021111915574510000_BST-2019-1010C16","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.stem.2009.04.002","article-title":"The role of Scgb1a1+ clara cells in the long-term maintenance and repair of lung airway, but not alveolar, epithelium","volume":"4","year":"2009","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C17","doi-asserted-by":"publisher","first-page":"2914","DOI":"10.1172\/JCI39731","article-title":"SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production","volume":"119","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2021111915574510000_BST-2019-1010C18","doi-asserted-by":"publisher","first-page":"e00966","DOI":"10.7554\/eLife.00966","article-title":"Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors","volume":"2","year":"2013","journal-title":"eLife"},{"key":"2021111915574510000_BST-2019-1010C19","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.stem.2017.04.003","article-title":"Deconstructing olfactory stem cell trajectories at single-cell resolution","volume":"20","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1038\/s41590-017-0001-2","article-title":"Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells","volume":"19","year":"2018","journal-title":"Nat. Immunol."},{"key":"2021111915574510000_BST-2019-1010C21","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1038\/s41467-017-01560-x","article-title":"Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling","volume":"8","year":"2017","journal-title":"Nat. Commun."},{"key":"2021111915574510000_BST-2019-1010C22","doi-asserted-by":"publisher","first-page":"eaaq1723","DOI":"10.1126\/science.aaq1723","article-title":"Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics","volume":"360","year":"2018","journal-title":"Science"},{"key":"2021111915574510000_BST-2019-1010C23","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/s41467-019-08831-9","article-title":"An atlas of the aging lung mapped by single cell transcriptomics and deep tissue proteomics","volume":"10","year":"2019","journal-title":"Nat. Commun."},{"key":"2021111915574510000_BST-2019-1010C24","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/s41591-019-0468-5","article-title":"A cellular census of human lungs identifies novel cell states in health and in asthma","volume":"25","year":"2019","journal-title":"Nat. Med."},{"key":"2021111915574510000_BST-2019-1010C25","first-page":"dev177428","article-title":"Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures","volume":"146","year":"2019"},{"key":"2021111915574510000_BST-2019-1010C26","volume-title":"Culture of Mouse Tracheal Epithelial Cells","year":"2013"},{"key":"2021111915574510000_BST-2019-1010C27","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/s41586-018-0394-6","article-title":"A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte","volume":"560","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C28","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/nature13173","article-title":"Reconstructing lineage hierarchies of the distal lung epithelium using single-cell RNA-seq","volume":"509","year":"2014","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C29","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41586-018-0449-8","article-title":"Allergic inflammatory memory in human respiratory epithelial progenitor cells","volume":"560","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C30","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41467-018-07770-1","article-title":"Single cell RNA analysis identifies cellular heterogeneity and adaptive responses of the lung at birth","volume":"10","year":"2019","journal-title":"Nat. Commun."},{"key":"2021111915574510000_BST-2019-1010C31","doi-asserted-by":"publisher","first-page":"1517","DOI":"10.1164\/rccm.201712-2410OC","article-title":"Single-cell transcriptomic analysis of human lung provides insights into the pathobiology of pulmonary fibrosis","volume":"199","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021111915574510000_BST-2019-1010C32","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1164\/rccm.201710-2107OC","article-title":"Ontogeny and biology of human small airway epithelial club cells","volume":"198","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021111915574510000_BST-2019-1010C33","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s13059-017-1382-0","article-title":"SCANPY: large-scale single-cell gene expression data analysis","volume":"19","year":"2018","journal-title":"Genome Biol."},{"key":"2021111915574510000_BST-2019-1010C34","doi-asserted-by":"publisher","first-page":"7432","DOI":"10.1073\/pnas.0500896102","article-title":"Geometric diffusions as a tool for harmonic analysis and structure definition of data: multiscale methods","volume":"102","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021111915574510000_BST-2019-1010C35","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1093\/bioinformatics\/btx792","article-title":"SPRING: a kinetic interface for visualizing high dimensional single-cell expression data","volume":"34","year":"2018","journal-title":"Bioinformatics"},{"key":"2021111915574510000_BST-2019-1010C36","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","year":"2017","journal-title":"Nat. Methods"},{"key":"2021111915574510000_BST-2019-1010C37","doi-asserted-by":"publisher","first-page":"e54","DOI":"10.1093\/nar\/gkw1278","article-title":"SLICE: determining cell differentiation and lineage based on single cell entropy","volume":"45","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"2021111915574510000_BST-2019-1010C38","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1038\/nmeth.1315","article-title":"mRNA-Seq whole-transcriptome analysis of a single cell","volume":"6","year":"2009","journal-title":"Nat. Methods."},{"key":"2021111915574510000_BST-2019-1010C39","unstructured":"Davis,\n            S.\n          , Kutum,R., Zappia,L., Sorenson,J., Kiselev,V., Olivier,P.et al. (2018) seandavi\/awesome-single-cell: 2018-06-20-110.5281\/zenodo.1294021"},{"key":"2021111915574510000_BST-2019-1010C40","doi-asserted-by":"publisher","first-page":"e8746","DOI":"10.15252\/msb.20188746","article-title":"Current best practices in single-cell RNA-seq analysis: a tutorial","volume":"15","year":"2019","journal-title":"Mol. Syst. Biol."},{"key":"2021111915574510000_BST-2019-1010C41","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/s41587-019-0071-9","article-title":"A comparison of single-cell trajectory inference methods","volume":"37","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2021111915574510000_BST-2019-1010C42","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"2021111915574510000_BST-2019-1010C43","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1186\/s12864-018-4772-0","article-title":"Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics","volume":"19","year":"2018","journal-title":"BMC Genom."},{"key":"2021111915574510000_BST-2019-1010C44","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1038\/s41587-019-0068-4","article-title":"Characterization of cell fate probabilities in single-cell data with Palantir","volume":"37","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2021111915574510000_BST-2019-1010C45","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13059-019-1663-x","article-title":"PAGA: graph abstraction reconciles clustering with trajectory inference through a topology preserving map of single cells","volume":"20","year":"2019","journal-title":"Genome Biol."},{"key":"2021111915574510000_BST-2019-1010C46","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1038\/s41586-018-0414-6","article-title":"RNA velocity of single cells","volume":"560","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C47","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1016\/j.stem.2018.03.018","article-title":"Myoepithelial cells of submucosal glands can function as reserve stem cells to regenerate airways after injury","volume":"22","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C48","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1242\/dev.116855","article-title":"Notch3-Jagged signaling controls the pool of undifferentiated airway progenitors","volume":"142","year":"2015","journal-title":"Development"},{"key":"2021111915574510000_BST-2019-1010C49","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.stem.2016.05.012","article-title":"Dual SMAD signaling inhibition enables long-term expansion of diverse epithelial basal cells","volume":"19","year":"2016","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C50","doi-asserted-by":"publisher","first-page":"4668","DOI":"10.1038\/s41467-018-06768-z","article-title":"CDC20B is required for deuterosome-mediated centriole production in multiciliated cells","volume":"9","year":"2018","journal-title":"Nat. Commun."},{"key":"2021111915574510000_BST-2019-1010C51","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.stem.2018.04.014","article-title":"Single-cell transcriptomics meets lineage tracing","volume":"23","year":"2018","journal-title":"Cell Stem Cell"},{"key":"2021111915574510000_BST-2019-1010C52","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nbt.4124","article-title":"Simultaneous lineage tracing and cell-type identification using CrIsPr-Cas9-induced genetic scars","volume":"36","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2021111915574510000_BST-2019-1010C53","doi-asserted-by":"publisher","first-page":"aaf7907","DOI":"10.1126\/science.aaf7907","article-title":"Whole organism lineage tracing by combinatorial and cumulative genome editing","volume":"353","year":"2016","journal-title":"Science"},{"key":"2021111915574510000_BST-2019-1010C54","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/nature25969","article-title":"Whole-organism clone tracing using single-cell sequencing","volume":"556","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C55","doi-asserted-by":"publisher","first-page":"eaat9804","DOI":"10.1126\/science.aat9804","article-title":"Developmental barcoding of whole mouse via homing CRISPR","volume":"361","year":"2018","journal-title":"Science"},{"key":"2021111915574510000_BST-2019-1010C56","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/s41586-018-0744-4","article-title":"Single-cell mapping of lineage and identity in direct reprogramming","volume":"564","year":"2018","journal-title":"Nature"},{"key":"2021111915574510000_BST-2019-1010C57","doi-asserted-by":"publisher","first-page":"dev177428","DOI":"10.1242\/dev.177428","article-title":"Novel dynamics of human mucociliary differentiation revealed by single-cell RNA sequencing of nasal epithelial cultures","volume":"146","year":"2019","journal-title":"Development."},{"key":"2021111915574510000_BST-2019-1010C58","doi-asserted-by":"publisher","DOI":"10.1101\/385328","article-title":"Palantir characterizes cell fate continuities in human hematopoiesis","year":"2018","journal-title":"bioRxiv"}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/48\/1\/327\/868692\/bst-2019-1010.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/48\/1\/327\/868692\/bst-2019-1010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T16:10:46Z","timestamp":1637338246000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/48\/1\/327\/221838\/Using-single-cell-RNA-sequencing-to-unravel-cell"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,10]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1,10]]},"published-print":{"date-parts":[[2020,2,28]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20191010","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,10]]}}}