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人类小胶质细胞转录组分析揭示灰质-白质异质性和多发性硬化症相关变化。

Transcriptional profiling of human microglia reveals grey-white matter heterogeneity and multiple sclerosis-associated changes.

机构信息

Neuroimmunology Research Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105BA, Amsterdam, The Netherlands.

Genomics and Immunoregulation, LIMES Institute, University of Bonn, Carl-Troll-Straße 31, 53115, Bonn, Germany.

出版信息

Nat Commun. 2019 Mar 13;10(1):1139. doi: 10.1038/s41467-019-08976-7.

DOI:10.1038/s41467-019-08976-7
PMID:30867424
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6416318/
Abstract

Here we report the transcriptional profile of human microglia, isolated from normal-appearing grey matter (GM) and white matter (WM) of multiple sclerosis (MS) and non-neurological control donors, to find possible early changes related to MS pathology. Microglia show a clear region-specific profile, indicated by higher expression of type-I interferon genes in GM and higher expression of NF-κB pathway genes in WM. Transcriptional changes in MS microglia also differ between GM and WM. MS WM microglia show increased lipid metabolism gene expression, which relates to MS pathology since active MS lesion-derived microglial nuclei show similar altered gene expression. Microglia from MS GM show increased expression of genes associated with glycolysis and iron homeostasis, possibly reflecting microglia reacting to iron depositions. Except for ADGRG1/GPR56, expression of homeostatic genes, such as P2RY12 and TMEM119, is unaltered in normal-appearing MS tissue, demonstrating overall preservation of microglia homeostatic functions in the initiation phase of MS.

摘要

我们在此报告了从小脑正常灰质（GM）和白质（WM）中分离出的人类小胶质细胞的转录谱，这些小胶质细胞来自多发性硬化症（MS）和非神经学对照供体，以寻找可能与 MS 病理学相关的早期变化。小胶质细胞表现出明显的区域特异性特征，GM 中 I 型干扰素基因的表达较高，WM 中 NF-κB 通路基因的表达较高。MS 小胶质细胞的转录变化在 GM 和 WM 之间也不同。MS WM 小胶质细胞表现出脂质代谢基因表达增加，这与 MS 病理学有关，因为活性 MS 病变衍生的小胶质细胞核显示出类似的改变基因表达。MS GM 中的小胶质细胞表现出与糖酵解和铁稳态相关的基因表达增加，这可能反映了小胶质细胞对铁沉积的反应。除了 ADGRG1/GPR56 外，正常 MS 组织中稳态基因（如 P2RY12 和 TMEM119）的表达没有改变，表明在 MS 的起始阶段，小胶质细胞的稳态功能总体上得到了保留。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/d91fa7828383/41467_2019_8976_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/e7753e455842/41467_2019_8976_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/adfeb62ced4e/41467_2019_8976_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/96a2ef60a364/41467_2019_8976_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/05b97c44c624/41467_2019_8976_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/d91fa7828383/41467_2019_8976_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/e7753e455842/41467_2019_8976_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/adfeb62ced4e/41467_2019_8976_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/96a2ef60a364/41467_2019_8976_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/05b97c44c624/41467_2019_8976_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/12db/6416318/d91fa7828383/41467_2019_8976_Fig5_HTML.jpg

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