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. 2021 May 27;19:63. doi: 10.1186/s12964-021-00740-z

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© The Author(s) 2021

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 1 — Airway epithelial differentiation pathways. a Differentiation of airway epithelial cells during embryonic development. b Differentiation of airway epithelial cells after birth (from adult stem cells). Names below the different cell types are the markers of the specific cell types (based on recent human single-cell RNAseq studies [21, 24]). TP63, KRT5, KRT6C, KRT14 and KRT15 are basal cell markers, while supra-basal cells are characterized by expression of KRT4, KRT13, KRT16 and KRT23. Within the mucociliary lineage, club cells are distinguished by expression of Scgb1a1, KRT7 and KRT19, mature goblet cells have expression of SPDEF, FOXQ1 and MUC5AC. The deuterosomal cells express PLK4, CCNO, CEP78 and DEUP1, while mature ciliated cells are distinguished by the expression of DNAH5, SPEF2, PIFO and LRRC6. Suprabasal cells can give rise to tuft cells, which express POUF2F3 and TRPM5. These in turn can differentiate either to ionocytes, expressing FOXI1 or CFTR, or to neuroendocrine cells, expressing PSMD5 or NGF