Vascularized human cortical organoids (vOrganoids) model cortical development in vivo
Vascularized human cortical organoids (vOrganoids) model cortical development in vivo
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DOI：
10.1371/journal.pbio.3000705
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发表时间：
2020-05-01
期刊：
影响因子：
9.8
通讯作者：
Wang, Xiaoqun
中科院分区：
文献类型：
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作者：
Shi, Yingchao;Sun, Le;Wang, Xiaoqun
对神经前体细胞的增殖和分化过程进行建模以产生成熟的皮质神经元亚型，对于研究人脑发育和寻找潜在的细胞治疗方法是至关重要的。我们展示了一种由典型的人类皮质细胞类型和血管结构组成的血管化类器官(VOrganids)产生的新范式，作为血管化和功能性脑器官模型超过200天。观察到自发性兴奋性突触后电流(SEPSCs)、自发性抑制性突触后电流(SIPSCs)和双向电传递，表明vOrganid内存在化学突触和电突触。更重要的是，单细胞RNA测序分析表明，vOrganids具有强大的神经发生能力，并且vOrganids的细胞差异表达与血管形态发生相关的基因(Deg)。将vOrganid移植到小鼠的S1皮质中，可以在移植物中构建起功能性的人-鼠血管，从而促进移植物中的细胞存活。这种vOrganid培养方法不仅可以作为研究人类皮质发育和探索脑部疾病病理的模型，而且为神经系统疾病和损伤的新的细胞治疗提供了潜在的前景。
Modeling the processes of neuronal progenitor proliferation and differentiation to produce mature cortical neuron subtypes is essential for the study of human brain development and the search for potential cell therapies. We demonstrated a novel paradigm for the generation of vascularized organoids (vOrganoids) consisting of typical human cortical cell types and a vascular structure for over 200 days as a vascularized and functional brain organoid model. The observation of spontaneous excitatory postsynaptic currents (sEPSCs), spontaneous inhibitory postsynaptic currents (sIPSCs), and bidirectional electrical transmission indicated the presence of chemical and electrical synapses in vOrganoids. More importantly, single-cell RNA-sequencing analysis illustrated that vOrganoids exhibited robust neurogenesis and that cells of vOrganoids differentially expressed genes (DEGs) related to blood vessel morphogenesis. The transplantation of vOrganoids into the mouse S1 cortex resulted in the construction of functional human-mouse blood vessels in the grafts that promoted cell survival in the grafts. This vOrganoid culture method could not only serve as a model to study human cortical development and explore brain disease pathology but also provide potential prospects for new cell therapies for nervous system disorders and injury.