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. 2021 Nov 19;27(3):1552–1561. doi: 10.1038/s41380-021-01372-y

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© The Author(s) 2021

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 Expression of canonical components of PNNs according to cell type, derived from single-nucleus RNA sequencing of 34 human dlPFC (BA9) samples [20]. OPCs consistently express higher levels of most of these components compared to other cell types. B Representative images of FISH validation of VCAN (Versican, yellow) expression in OPCs (PDGFRA+ cells, white). Note the VCAN-expressing OPC juxtaposed to a PVALB+ (magenta) cell. Nuclei were counterstained with DAPI (blue). Scale bar = 5 µm. C Representative images of FISH validation of PTPRZ1 (Phosphacan, yellow) expression in OPCs (PDGFRA+ cells, white). Nuclei were counterstained with DAPI (blue). Scale bar = 5 µm. D Both VCAN (left) and PTPRZ1 (right) expression is highly enriched in OPCs, with 97.8% of VCAN+ cells (N = 225) co-expressing PDGFRA and 91.8% of PTPRZ1+ cells (N = 281) co-expressing PDGFRA. E Representative image of versican (green) immunolabeling. Despite enrichment of VCAN gene in OPCs, the versican protein shows a characteristic PNN staining pattern and colocalized with WFL (red). Nuclei were counterstained with DAPI (blue). Scale bar = 25 µm. F The average expression of VCAN in OPCs was significantly higher in DS-CA subjects (N = 139 cells, 7 subjects) compared to CTRLs (N = 160 cells, 8 subjects) and DS (N = 119 cells, 6 subjects) (one-way ANOVA F(2, 415) = 17.25, P < 0.0001, followed by Tukey’s multiple comparison test). G The average expression of PTPRZ1 in OPCs was significantly higher in DS-CA subjects (N = 63 cells, 4 subjects) compared to CTRLs (N = 117 cells, 6 subjects) and DS (N = 81 cells, 5 subjects) (one-way ANOVA F(2, 258) = 31.65, P < 0.0001, followed by Tukey’s multiple comparison test). H The average expression of TNR in OPCs was significantly higher in DS-CA subjects (N = 200 cells, 8 subjects) compared to CTRLs (N = 207 cells, 7 subjects) and DS (N = 160 cells, 5 subjects) (one-way ANOVA, F(2, 564) = 18.69, P < 0.0001, followed by Tukey’s multiple comparison test). Both PTPRZ1 (I) and TNR (J), but not VCAN (K) average expression in OPCs modestly correlated with PNNs densities (R² = 0.35, P = 0.025 and R² = 0.28, P = 0.022, respectively). L A negative correlation was found between average distance of OPCs from closest PVALB+ cell and PNNs density (R² = 0.36, P = 0.024), suggesting that OPCs proximity with PVALB+ cells could be associated with changes in PNN density. M Proximity of OPCs with PVALB+ cells was increased in DS-CA subjects (N = 90 OPCs, 5 subjects) compared to CTRLs (N = 106 OPCs, 6 subjects) and DS (N = 73 OPCs, 4 subjects) (one-way ANOVA: F(2, 266) = 7.963, P = 0.0004, followed by Tukey’s multiple comparison test). N Average densities of PDGFRA+ OPCs were not changed between DS-CA (N = 8), DS (N = 7), and CTRL (N = 6) groups (Kruskal–Wallis ANOVA, H(2,21) = 4.67, P = 0.095).