Actin cytoskeleton dynamics in stem cells from autistic individuals.
Actin cytoskeleton dynamics in stem cells from autistic individuals.
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DOI：
10.1038/s41598-018-29309-6
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发表时间：
2018-07-24
影响因子：
4.6
通讯作者：
Passos-Bueno MR
中科院分区：
文献类型：
--
作者：
Griesi-Oliveira K;Suzuki AM;Alves AY;Mafra ACCN;Yamamoto GL;Ezquina S;Magalhães YT;Forti FL;Sertie AL;Zachi EC;Vadasz E;Passos-Bueno MR
一系列间接证据，如细胞骨架相关基因的突变或表达失调，表明细胞骨架动力学在自闭症谱系障碍(ASD)中受到损害，细胞骨架动力学是轴突和树突发育所必需的过程。然而，还没有研究检查ASD患者细胞中的细胞骨架动力学是否发生了功能性改变。本研究通过诱导肌动蛋白细丝解聚，然后检测RhoGTP酶Rac、CDC42或RhoA的激活，研究了13例ASD患者和8名对照组的人脱落乳牙干细胞中肌动蛋白细胞骨架动力学的调节。我们观察到来自7名ASD患者(53%)的干细胞表现出细丝重建的动态变化，包括我们小组最近研究的一名患者，他的IPSC来源的神经细胞显示出较短和较少的树枝状突起。我们还报告了潜在的致病遗传变异，这些变异可能与在一些患者来源的细胞中观察到的肌动蛋白重聚合动力学的变化有关。我们的结果表明，至少对于ASD患者的一部分患者来说，肌动蛋白聚合的动力学受到了损害，这可能最终导致神经元异常。
Several lines of indirect evidence, such as mutations or dysregulated expression of genes related to cytoskeleton, have suggested that cytoskeletal dynamics, a process essential for axons and dendrites development, is compromised in autism spectrum disorders (ASD). However, no study has yet examined whether cytoskeleton dynamics is functionally altered in cells from ASD patients. Here we investigated the regulation of actin cytoskeleton dynamics in stem cells from human exfoliated deciduous teeth (SHEDs) of 13 ASD patients and 8 control individuals by inducing actin filament depolymerization and then measuing their reconstruction upon activation of the RhoGTPases Rac, Cdc42 or RhoA. We observed that stem cells from seven ASD individuals (53%) presented altered dymanics of filament reconstruction, including a patient recently studied by our group whose iPSC-derived neuronal cells show shorten and less arborized neurites. We also report potentially pathogenic genetic variants that might be related to the alterations in actin repolymerization dynamics observed in some patient-derived cells. Our results suggest that, at least for a subgroup of ASD patients, the dynamics of actin polymerization is impaired, which might be ultimately leading to neuronal abnormalities.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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通讯作者：
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