Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.
Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.
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DOI：
10.1242/dmm.049418
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发表时间：
2022-09-01
影响因子：
4.3
通讯作者：
Scotter, Emma L.
中科院分区：
文献类型：
--
作者：
Cao, Maize C.;Scotter, Emma L.
关键词：
TDP-43 蛋白病是肌萎缩侧索硬化症 (ALS) 和 tau 阴性额颞叶痴呆 (FTD) 的主要病理。越来越多的证据表明，正常 TDP-43 RNA 加工功能的丧失是一个关键的病理机制。然而，TDP-43 的 RNA 靶标因报道而异，并且从未在模型和疾病之间进行正式整理或比较，这阻碍了对 TDP-43 功能的理解。在这里，我们对来自六个 TDP-43 敲低模型的公开 RNA 测序数据集和来自 ALS/FTD 大脑的 TDP-43 免疫阴性神经元核进行了重新分析和荟萃分析，以识别差异表达基因 (DEG) 和差异外显子使用 (DEU) 事件。敲低模型之间的 DEG 几乎没有重叠，但 PFKP、STMN2、CFP、KIAA1324 和 TRHDE 是共同靶标，并且在 TDP-43 免疫阴性神经元中也有差异表达。 DEG 富集分析揭示了多种生物学途径，包括免疫和突触功能。人类数据集中常见的 DEU 事件包括众所周知的目标 POLDIP3 和 STMN2，以及新目标 EXD3、MMAB、DLG5 和 GOSR2。我们的交互式数据库 () 允许进一步探索 TDP-43 DEG 和 DEU 目标。这些数据共同确定了可用于治疗或验证功能丧失过程的 TDP-43 靶点。 。摘要：TDP-43 靶基因和剪接事件的荟萃分析和交互式数据库是在公开的 RNA 测序数据集中从肌萎缩侧索硬化症/额颞叶痴呆的 6 个 TDP-43 敲低模型和 TDP-43 免疫阴性神经元中确定的。
TDP-43 proteinopathy is the major pathology in amyotrophic lateral sclerosis (ALS) and tau-negative frontotemporal dementia (FTD). Mounting evidence implicates loss of normal TDP-43 RNA-processing function as a key pathomechanism. However, the RNA targets of TDP-43 differ by report, and have never been formally collated or compared between models and disease, hampering understanding of TDP-43 function. Here, we conducted re-analysis and meta-analysis of publicly available RNA-sequencing datasets from six TDP-43-knockdown models, and TDP-43-immunonegative neuronal nuclei from ALS/FTD brain, to identify differentially expressed genes (DEGs) and differential exon usage (DEU) events. There was little overlap in DEGs between knockdown models, but PFKP, STMN2, CFP, KIAA1324 and TRHDE were common targets and were also differentially expressed in TDP-43-immunonegative neurons. DEG enrichment analysis revealed diverse biological pathways including immune and synaptic functions. Common DEU events in human datasets included well-known targets POLDIP3 and STMN2, and novel targets EXD3, MMAB, DLG5 and GOSR2. Our interactive database () allows further exploration of TDP-43 DEG and DEU targets. Together, these data identify TDP-43 targets that can be exploited therapeutically or used to validate loss-of-function processes. . Summary: A meta-analysis and interactive database of TDP-43 target genes and splicing events identified in publicly available RNA-sequencing datasets from six TDP-43 knockdown models and TDP-43-immunonegative neurons in amyotrophic lateral sclerosis/frontotemporal dementia.
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影响因子：
4.4
作者：
Arnone JT;Robbins-Pianka A;Arace JR;Kass-Gergi S;McAlear MA
通讯作者：
McAlear MA
影响因子：
17.1
作者：
通讯作者：
--
影响因子：
64.8
作者：
Ansarullah;Jain, Chirag;Lickert, Heiko
通讯作者：
Lickert, Heiko
影响因子：
64.8
作者：
Berkovits BD;Mayr C
通讯作者：
Mayr C
影响因子：
12.7
作者：
Arai, Tetsuaki;Mackenzie, Ian R. A.;Akiyama, Haruhiko
通讯作者：
Akiyama, Haruhiko