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小鼠视网膜色素上皮细胞对低剂量阿霉素反应的单细胞转录组。

Single-cell transcriptome of the mouse retinal pigment epithelium in response to a low-dose of doxorubicin.

机构信息

Department of Ophthalmology, Konkuk University School of Medicine, Seoul, Republic of Korea.

Department of Ophthalmology, Konkuk University Medical Center, Seoul, Republic of Korea.

出版信息

Commun Biol. 2022 Jul 20;5(1):722. doi: 10.1038/s42003-022-03676-3.

DOI:10.1038/s42003-022-03676-3
PMID:35859009
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9300683/
Abstract

Cellular senescence of the retinal pigment epithelium (RPE) is thought to play an important role in vision-threatening retinal degenerative diseases, such as age-related macular degeneration (AMD). However, the single-cell RNA profiles of control RPE tissue and RPE tissue exhibiting cellular senescence are not well known. We have analyzed the single-cell transcriptomes of control mice and mice with low-dose doxorubicin (Dox)-induced RPE senescence (Dox-RPE). Our results have identified 4 main subpopulations in the control RPE that exhibit heterogeneous biological activities and play roles in ATP synthesis, cell mobility/differentiation, mRNA processing, and catalytic activity. In Dox-RPE mice, cellular senescence mainly occurs in the specific cluster, which has been characterized by catalytic activity in the control RPE. Furthermore, in the Dox-RPE mice, 6 genes that have not previously been associated with senescence also show altered expression in 4 clusters. Our results might serve as a useful reference for the study of control and senescent RPE.

摘要

视网膜色素上皮 (RPE) 的细胞衰老被认为在威胁视力的视网膜退行性疾病中起重要作用,例如年龄相关性黄斑变性 (AMD)。然而,表现出细胞衰老的对照 RPE 组织和 RPE 组织的单细胞 RNA 图谱尚不清楚。我们已经分析了对照小鼠和接受低剂量阿霉素 (Dox) 诱导的 RPE 衰老 (Dox-RPE) 的小鼠的单细胞转录组。我们的结果在对照 RPE 中确定了 4 个主要亚群,它们表现出不同的生物活性,在 ATP 合成、细胞迁移/分化、mRNA 处理和催化活性中发挥作用。在 Dox-RPE 小鼠中,细胞衰老主要发生在对照 RPE 中具有催化活性的特定簇中。此外,在 Dox-RPE 小鼠中,先前与衰老无关的 6 个基因在 4 个簇中也表现出改变的表达。我们的结果可能为对照和衰老的 RPE 研究提供有用的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/e7d99d308ca5/42003_2022_3676_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/5b0f66984082/42003_2022_3676_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/9c171ccc1225/42003_2022_3676_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/2b05719fe21c/42003_2022_3676_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/eb061f539172/42003_2022_3676_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/c2ca912c0e09/42003_2022_3676_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/e7d99d308ca5/42003_2022_3676_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/5b0f66984082/42003_2022_3676_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/9c171ccc1225/42003_2022_3676_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/2b05719fe21c/42003_2022_3676_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/eb061f539172/42003_2022_3676_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/c2ca912c0e09/42003_2022_3676_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f45a/9300683/e7d99d308ca5/42003_2022_3676_Fig6_HTML.jpg

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