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Probing impaired neurogenesis in human brain organoids exposed to alcohol
Integrative Biology ( IF 1.5 ) Pub Date : 2017-11-23 , DOI: 10.1039/c7ib00105c Yujuan Zhu 1, 2, 3, 4, 5 , Li Wang 1, 2, 3, 4, 6 , Fangchao Yin 1, 2, 3, 4, 5 , Yue Yu 1, 2, 3, 4, 5 , Yaqing Wang 1, 2, 3, 4, 5 , Matthew J. Shepard 7, 8, 9, 10, 11 , Zhengping Zhuang 7, 8, 9, 10 , Jianhua Qin 1, 2, 3, 4, 5
Integrative Biology ( IF 1.5 ) Pub Date : 2017-11-23 , DOI: 10.1039/c7ib00105c Yujuan Zhu 1, 2, 3, 4, 5 , Li Wang 1, 2, 3, 4, 6 , Fangchao Yin 1, 2, 3, 4, 5 , Yue Yu 1, 2, 3, 4, 5 , Yaqing Wang 1, 2, 3, 4, 5 , Matthew J. Shepard 7, 8, 9, 10, 11 , Zhengping Zhuang 7, 8, 9, 10 , Jianhua Qin 1, 2, 3, 4, 5
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The fetal brain is highly vulnerable to ethanol exposure, which can trigger various long-term neuronal disabilities and cognitive dysfunctions. However, a comprehensive understanding of fetal brain development under ethanol exposure is challenging due to the limitations of animal models. Here, we propose a human induced pluripotent stem cell (hiPSC)-based 3D brain organoid model, and explore the mechanisms underlying neural dysfunctions in prenatal alcohol exposure (PAE) in vitro. Brain organoids were examined to resemble brain organogenesis in vivo at early stages during gestation, with specific features of neuronal differentiation, brain regionalization, and cortical organization. With ethanol exposure, the brain organoids displayed attenuated neurite outgrowth and skewed neural maturation. Transcriptome analysis identified a series of new markedly altered genes and enriched pathways, such as GSX2, RSPO2, and the Hippo signaling pathway. These genes or pathways, to our knowledge, were reported to be involved in ethanol-induced impaired neurogenesis for the first time. Our new findings might facilitate better understanding of the various postnatal neural disorders observed in individuals with PAE.
中文翻译：
探索暴露于酒精的人脑类器官中受损的神经发生
胎儿的大脑极易受到乙醇的暴露，这会引发各种长期的神经元残疾和认知功能障碍。然而，由于动物模型的局限性，对乙醇暴露下胎儿大脑发育的全面理解具有挑战性。在这里，我们提出了一个基于人类诱导的多能干细胞（hiPSC）的3D脑类器官模型，并探讨了在产前酒精暴露（PAE）中神经功能障碍的潜在机制。检查了脑类器官器官，使其在体内类似于脑器官发生在妊娠早期，具有神经元分化，脑区域化和皮层组织的特定特征。在暴露于乙醇的情况下，大脑的类器官表现出减弱的神经突增生和偏斜的神经成熟。转录组分析确定了一系列新的显着改变的基因和丰富的途径，例如GSX2，RSPO2和Hippo信号通路。据我们所知，这些基因或途径首次被报道与乙醇诱导的神经发生受损有关。我们的新发现可能有助于更好地了解在PAE患者中观察到的各种产后神经疾病。
更新日期：2017-11-23
中文翻译：
探索暴露于酒精的人脑类器官中受损的神经发生
胎儿的大脑极易受到乙醇的暴露，这会引发各种长期的神经元残疾和认知功能障碍。然而，由于动物模型的局限性，对乙醇暴露下胎儿大脑发育的全面理解具有挑战性。在这里，我们提出了一个基于人类诱导的多能干细胞（hiPSC）的3D脑类器官模型，并探讨了在产前酒精暴露（PAE）中神经功能障碍的潜在机制。检查了脑类器官器官，使其在体内类似于脑器官发生在妊娠早期，具有神经元分化，脑区域化和皮层组织的特定特征。在暴露于乙醇的情况下，大脑的类器官表现出减弱的神经突增生和偏斜的神经成熟。转录组分析确定了一系列新的显着改变的基因和丰富的途径，例如GSX2，RSPO2和Hippo信号通路。据我们所知，这些基因或途径首次被报道与乙醇诱导的神经发生受损有关。我们的新发现可能有助于更好地了解在PAE患者中观察到的各种产后神经疾病。
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