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. 2023 Jan 11;11:6. doi: 10.1186/s40478-022-01496-4

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© The Author(s) 2023

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. 4 — Deposits of sulphur-containing species in SHH nodules are likely to be a combination of small leucine rich proteoglycans including lumican. a and b Small leucine rich proteoglycans (SLRPs) and other collagens are correlated with high COL1A1 and COL6A1 expression in SHH patients in the Cavalli data set (Cavalli et al. [21], SHH: n = 223, log-rank test used to establish ‘high’ and ‘low’ expression; one-way ANOVA, grey dots represent samples where p ≥ 0.05 and navy dots where p < 0.05) c scRNAseq analysis revealed that LUM (a SLRP) is expressed by 25% of cells within SHH nodules and that 70% of these cells also express ECM genes of interest (purple: gene expressing cell; grey: non-expressing cell; percentage indicates relative proportion of total cells expressing the specified gene and percentage ‘shared’ indicates the proportion of LUM expressing cells that also express the ECM genes COL6A1, COL6A2, COL6A3, COL1A1 and TNC. d Immunohistochemical staining of ONS76 and HD-MB03 hydrogel nodules for lumican reveals that lumican is specifically located on the outer edge of SHH nodules (similar to type-I and type-VI collagens) and is not present in Group 3 nodules