Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.
Protein interaction studies in human induced neurons indicate convergent biology underlying autism spectrum disorders.
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DOI：
10.1016/j.xgen.2022.100250
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发表时间：
2023-03-08
期刊：
影响因子：
--
通讯作者：
Lage, Kasper
中科院分区：
文献类型：
--
作者：
Pintacuda, Greta;Hsu, Yu-Han H.;Tsafou, Kalliopi;Li, Ka Wan;Martin, Jacqueline M.;Riseman, Jackson;Biagini, Julia C.;Ching, Joshua K. T.;Mena, Daya;Gonzalez-Lozano, Miguel A.;Egri, Shawn B.;Jaffe, Jake;Smit, August B.;Fornelos, Nadine;Eggan, Kevin C.;Lage, Kasper
自闭症谱系障碍（ASD）与大脑中丰富表达的基因有关，但目前尚不清楚这些基因如何汇聚成细胞类型特异性网络。我们建立了一个蛋白质-蛋白质相互作用网络的13 ASD相关基因在人类兴奋性神经元来源于诱导多能干细胞（iPSC）。该网络包含新报道的相互作用，并丰富了在ASD患者中观察到的遗传和转录干扰。我们利用网络数据表明，ASD相关的脑特异性ANK 2亚型对于其与突触蛋白的相互作用非常重要，并表征了影响神经元生长的PTEN-AKAP 8L相互作用。IGF 2BP 1 -3复合物作为网络中的汇聚点出现，可以调节ASD相关基因的转录回路。我们的研究结果展示了细胞类型特异性相互作用组作为补充遗传和转录组数据的框架，并说明了个体和聚合相互作用如何导致对ASD的生物学见解。人类神经元中13个自闭症基因的蛋白质-蛋白质相互作用网络该网络包含新报道的，可重复的和大脑相关的相互作用该网络富含与自闭症相关的遗传和转录信号。在人类iPSC衍生的诱导神经元中为13个自闭症相关基因生成了一个蛋白质-蛋白质相互作用网络，并表明它包含许多新报道的，可重复的相互作用，这些相互作用可能指向自闭症的大脑特异性机制。他们的发现强调了使用细胞类型特异性蛋白质相互作用组来理解神经精神疾病的潜力。
Autism spectrum disorders (ASDs) have been linked to genes with enriched expression in the brain, but it is unclear how these genes converge into cell-type-specific networks. We built a protein-protein interaction network for 13 ASD-associated genes in human excitatory neurons derived from induced pluripotent stem cells (iPSCs). The network contains newly reported interactions and is enriched for genetic and transcriptional perturbations observed in individuals with ASDs. We leveraged the network data to show that the ASD-linked brain-specific isoform of ANK2 is important for its interactions with synaptic proteins and to characterize a PTEN-AKAP8L interaction that influences neuronal growth. The IGF2BP1-3 complex emerged as a convergent point in the network that may regulate a transcriptional circuit of ASD-associated genes. Our findings showcase cell-type-specific interactomes as a framework to complement genetic and transcriptomic data and illustrate how both individual and convergent interactions can lead to biological insights into ASDs. Protein-protein interaction network for 13 autism genes in human neurons The network contains newly reported, reproducible, and brain-relevant interactions The network is enriched for genetic and transcriptional signals linked to autism Both individual and convergent interactions can reveal mechanisms underlying autism Pintacuda et al. generated a protein-protein interaction network for 13 autism-associated genes in human iPSC-derived induced neurons and showed that it contains many newly reported, reproducible interactions that could point to brain-specific mechanisms underlying autism. Their findings highlight the potential of using cell-type-specific protein interactomes to understand neuropsychiatric disorders.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.8
作者：
Finucane HK;Reshef YA;Anttila V;Slowikowski K;Gusev A;Byrnes A;Gazal S;Loh PR;Lareau C;Shoresh N;Genovese G;Saunders A;Macosko E;Pollack S;Brainstorm Consortium;Perry JRB;Buenrostro JD;Bernstein BE;Raychaudhuri S;McCarroll S;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
自闭症谱系障碍（ASD）、精神分裂症和双相情感障碍中全转录组异构体水平失调
影响因子：
56.9
作者：
Gandal, Michael J.;Zhang, Pan;Geschwind, Daniel H.
通讯作者：
Geschwind, Daniel H.
影响因子：
82.9
作者：
Chen, Chien-Ju;Sgritta, Martina;Costa-Mattioli, Mauro
通讯作者：
Costa-Mattioli, Mauro