当前位置: X-MOL 学术Acta Neuropathol. Commun. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Transcriptional profiling of multiple system atrophy cerebellar tissue highlights differences between the parkinsonian and cerebellar sub-types of the disease.
Acta Neuropathologica Communications ( IF 6.2 ) Pub Date : 2020-06-03 , DOI: 10.1186/s40478-020-00950-5
Ignazio S Piras 1 , Christiane Bleul 1 , Isabelle Schrauwen 1, 2 , Joshua Talboom 1 , Lorida Llaci 1, 3 , Matthew D De Both 1 , Marcus A Naymik 1 , Glenda Halliday 4 , Conceicao Bettencourt 5 , Janice L Holton 5 , Geidy E Serrano 6 , Lucia I Sue 6 , Thomas G Beach 6 , Nadia Stefanova 7 , Matthew J Huentelman 1
Affiliation  

Multiple system atrophy (MSA) is a rare adult-onset neurodegenerative disease of unknown cause, with no effective therapeutic options, and no cure. Limited work to date has attempted to characterize the transcriptional changes associated with the disease, which presents as either predominating parkinsonian (MSA-P) or cerebellar (MSC-C) symptoms. We report here the results of RNA expression profiling of cerebellar white matter (CWM) tissue from two independent cohorts of MSA patients (n = 66) and healthy controls (HC; n = 66). RNA samples from bulk brain tissue and from oligodendrocytes obtained by laser capture microdissection (LCM) were sequenced. Differentially expressed genes (DEGs) were obtained and were examined before and after stratifying by MSA clinical sub-type. We detected the highest number of DEGs in the MSA-C group (n = 747) while only one gene was noted in MSA-P, highlighting the larger dysregulation of the transcriptome in the MSA-C CWM. Results from both bulk tissue and LCM analysis showed a downregulation of oligodendrocyte genes and an enrichment for myelination processes with a key role noted for the QKI gene. Additionally, we observed a significant upregulation of neuron-specific gene expression in MSA-C and enrichment for synaptic processes. A third cluster of genes was associated with the upregulation of astrocyte and endothelial genes, two cell types with a key role in inflammation processes. Finally, network analysis in MSA-C showed enrichment for β-amyloid related functional classes, including the known Alzheimer’s disease (AD) genes, APP and PSEN1. This is the largest RNA profiling study ever conducted on post-mortem brain tissue from MSA patients. We were able to define specific gene expression signatures for MSA-C highlighting the different stages of the complex neurodegenerative cascade of the disease that included alterations in several cell-specific transcriptional programs. Finally, several results suggest a common transcriptional dysregulation between MSA and AD-related genes despite the clinical and neuropathological distinctions between the two diseases.

中文翻译:


多系统萎缩小脑组织的转录谱突显了该疾病的帕金森病亚型和小脑亚型之间的差异。



多系统萎缩(MSA)是一种罕见的成人发病的神经退行性疾病,原因不明,没有有效的治疗方案,也无法治愈。迄今为止,有限的工作试图描述与该疾病相关的转录变化,该疾病表现为主要帕金森病(MSA-P)或小脑(MSC-C)症状。我们在这里报告了两个独立的 MSA 患者组 (n = 66) 和健康对照 (HC; n = 66) 的小脑白质 (CWM) 组织的 RNA 表达谱结果。对来自大量脑组织和通过激光捕获显微切割 (LCM) 获得的少突胶质细胞的 RNA 样本进行了测序。获得差异表达基因 (DEG),并在按 MSA 临床亚型分层之前和之后进行检查。我们在 MSA-C 组中检测到最多数量的 DEG(n = 747),而在 MSA-P 中仅发现一个基因,这凸显了 MSA-C CWM 中转录组的更大失调。大块组织和 LCM 分析的结果显示少突胶质细胞基因下调,髓鞘形成过程富集,其中 QKI 基因发挥关键作用。此外,我们观察到 MSA-C 中神经元特异性基因表达的显着上调和突触过程的富集。第三组基因与星形胶质细胞和内皮细胞基因的上调有关,这两种细胞类型在炎症过程中发挥着关键作用。最后,MSA-C 中的网络分析显示 β-淀粉样蛋白相关功能类别的富集,包括已知的阿尔茨海默病 (AD) 基因、APP 和 PSEN1。这是迄今为止对 MSA 患者死后脑组织进行的最大规模的 RNA 分析研究。 我们能够定义 MSA-C 的特定基因表达特征,突出显示该疾病复杂的神经退行性级联的不同阶段,其中包括几个细胞特异性转录程序的改变。最后,一些结果表明,尽管这两种疾病之间存在临床和神经病理学差异,但 MSA 和 AD 相关基因之间存在常见的转录失调。
更新日期:2020-06-03
down
wechat
bug