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. 2022 Nov 21;19(2):177–183. doi: 10.1038/s41567-022-01822-6

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© The Author(s) 2022

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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Extended Data Fig. 6 — a, Workflow of experiment to test the role of lysophosphatidic acid (LPA) synthesis in organoid morphogenesis. Organoids were treated with varying concentrations of HA130, a small molecular inhibitor for ENPP2, with or without 250 nM retinoic acid (RA) during Day 2 to Day 4. Organoid morphologies were scored at Day 4. b, Representative examples of Day 4 organoids treated with varying concentrations of HA130 in the absence of RA. c, Representative examples of Day 4 organoids treated with varying concentrations of HA130 in the presence of RA. Images show maximum intensity projections of PODXL immunofluorescence signal. Organoid outer boundary (magenta) and apical surfaces (green) are shown for the corresponding sample. d, The temporal change in the number of lobules N normalized to the beginning of the movie for each organoid under the combination of RA and HA130 treatments. e, The temporal change in the total genus g of organoids under the combination of RA and HA130 treatments. The conditions +HA130 (n=3 organoids treated with 2000 nM HA130) and +RA, +HA130 (n=2 organoids treated with 250 nM RA and 2000 nM HA130) are presented together with the data for untreated and +RA conditions from Fig. 2. Scale bar, 100 μm.