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. 2023 Apr 21;33(6):421–433. doi: 10.1038/s41422-023-00802-6

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© The Author(s) 2023

Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a UMAP layout showing the integration of human epithelial scRNA-seq dataset from this study (colored by sample collection time points) and published datasets^9,13 (colored by gray). Upper (green arrow) and lower (magenta arrow) trajectories represent proximal and distal epithelial lineages, separately. b Illustration of TF–gene regulons, inferred by SCENIC. c Heatmap showing temporal changes of regulon activity in proximal (green) and distal (magenta) branches. The bar graph on the left represents the Normalized Enrichment Score (NES) of each TF. Genes marked in red are newly identified TFs in this study. d TF activity (green) and expression (red) of proximal-specific THRB and EGR3 (above) and distal-specific ETV1 and SOX6 (bottom) during weeks 4–8 are projected on UMAP. SCENIC-generated TF activity, represented by AUC score, reflects the co-expression strength of TF and its target genes. e Violin plots showing the expression of the SOX2, NFIB, GRHL1, SOX9, ETV5 and GATA6 in EPI_SOX2^hi/ETV5^lo and EPI_SOX9^hi/ETV5^hi cells from weeks 4–8. f Illustrations of the proximal–distal patterning and marker gene expression.