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. 2021 Jun 29;53(6):1092–1108. doi: 10.1038/s12276-021-00643-6

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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. 6 — a–c Network models showing interactions among DEGs involved in endocytosis and lysosomal degradation (a), nuclear transport and RNA processing (b), or nucleotide metabolism (c). Node colors represent the clusters to which the corresponding belong (see legend box). Gray lines denote protein-protein interactions, arrows represent the transport of molecules or metabolic reactions, the dotted line denotes the membrane of the nucleolus, and the two thick lines represent the plasma or nuclear membrane. Names of complexes or functional modules for the closely located genes are shown. d qRT-PCR analysis of representative genes in the cellular pathways common to both NBIS and RS. The analyzed genes are shown as large nodes in the network models (a–c). mRNA expression changes were first normalized to those of RPS11 (internal control) and then further normalized by the mean mRNA expression change in young HDFs. The values are presented as the means ± SD (n = 2 or 3). *, P < 0.05; **, P < 0.01; and ***, P < 0.001 by one-way analysis of variance with Dunnett’s post hoc test.