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Sci Adv 2023 Apr 07;914:eadd5745. doi: 10.1126/sciadv.add5745.
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A single-cell, time-resolved profiling of Xenopus mucociliary epithelium reveals nonhierarchical model of development.

Lee J , Møller AF , Chae S , Bussek A , Park TJ , Kim Y , Lee HS , Pers TH , Kwon T , Sedzinski J , Natarajan KN .

The specialized cell types of the mucociliary epithelium (MCE) lining the respiratory tract enable continuous airway clearing, with its defects leading to chronic respiratory diseases. The molecular mechanisms driving cell fate acquisition and temporal specialization during mucociliary epithelial development remain largely unknown. Here, we profile the developing Xenopus MCE from pluripotent to mature stages by single-cell transcriptomics, identifying multipotent early epithelial progenitors that execute multilineage cues before specializing into late-stage ionocytes and goblet and basal cells. Combining in silico lineage inference, in situ hybridization, and single-cell multiplexed RNA imaging, we capture the initial bifurcation into early epithelial and multiciliated progenitors and chart cell type emergence and fate progression into specialized cell types. Comparative analysis of nine airway atlases reveals an evolutionary conserved transcriptional module in ciliated cells, whereas secretory and basal types execute distinct function-specific programs across vertebrates. We uncover a continuous nonhierarchical model of MCE development alongside a data resource for understanding respiratory biology.

PubMed ID: 37027470
PMC ID: PMC10081853
Article link: Sci Adv

Species referenced: Xenopus laevis
Genes referenced: akna angpt4 anxa2 arid2 atf4 atp6v1b1 blvra bsg ca12 ca2 calr camk1 cav3.1 cftr cirbp ctbs dmrt2 dynll1 eef1a1o esrra foxa1 foxi1 foxj1 fucolectin-e gdf11.1 gfi1 grhl1 grhl3 h2ac1 has1 hes1 hes5.4 hic2 id2 id4 inhbc.2 itln1 krt18.1 mal2 mcc mcidas nkx2-3 notch1 notch2 otog otogl2 pbx2 pfn1 pou5f3 pou5f3.2 psmd6 rfx1 smad3 smad7 sox3 sp7 spdef tbx2 tbx3 tcf25 tef tekt2 tgfbr1 tmsb4x tp63 tubb4b usf1 ybx1 znf326 znf706l
Antibodies: Tuba4b Ab5

GEO Series: GSE158088: NCBI

Article Images: [+] show captions
References [+] :
Arason, deltaNp63 has a role in maintaining epithelial integrity in airway epithelium. 2014, Pubmed