Pluripotent Stem Cell-Derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins
Pluripotent Stem Cell-Derived Cerebral Organoids Reveal Human Oligodendrogenesis with Dorsal and Ventral Origins
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DOI：
10.1016/j.stemcr.2019.04.011
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发表时间：
2019-05-14
影响因子：
5.9
通讯作者：
Jiang, Peng
中科院分区：
文献类型：
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作者：
Kim, Hyosung;Xu, Ranjie;Jiang, Peng
在啮齿类动物的大脑中，少突胶质细胞发生的过程已经被相对较好地描绘出来。然而，目前还不清楚类似的发育过程是否在人类大脑中表现出来。在这里，我们报告了前脑类器官中的少突神经发生，通过使用OLIG 2-GFP敲入人多能干细胞（hPSC）报告细胞系产生。OLIG 2/GFP在腹侧前脑类器官（VFO）与背侧前脑类器官（DFO）中表现出不同的时间表达模式。有趣的是，在神经元成熟后，VFO和DFO都可以诱导少突神经元的发生。组装VFO和DFO以产生融合的前脑类器官（FFO）可促进少突胶质细胞成熟。此外，背侧来源的少突胶质细胞竞争优势腹侧来源的少突胶质细胞，并成为占主导地位的FFO后，长期培养。因此，我们的类器官模型揭示了人类少突胶质细胞的腹侧和背侧起源。这些模型将有助于研究人类腹侧和背侧来源的少突胶质细胞之间的表型和功能差异，并揭示与皮质髓鞘缺陷相关的疾病机制。
The process of oligodendrogenesis has been relatively well delineated in the rodent brain. However, it remains unknown whether analogous developmental processes are manifested in the human brain. Here we report oligodendrogenesis in forebrain organoids, generated by using OLIG2-GFP knockin human pluripotent stem cell (hPSC) reporter lines. OLIG2/GFP exhibits distinct temporal expression patterns in ventral forebrain organoids (VFOs) versus dorsal forebrain organoids (DFOs). Interestingly, oligodendrogenesis can be induced in both VFOs and DFOs after neuronal maturation. Assembling VFOs and DFOs to generate fused forebrain organoids (FFOs) promotes oligodendroglia maturation. Furthermore, dorsally derived oligodendroglial cells outcompete ventrally derived oligodendroglia and become dominant in FFOs after long-term culture. Thus, our organoid models reveal human oligodendrogenesis with ventral and dorsal origins. These models will serve to study the phenotypic and functional differences between human ventrally and dorsally derived oligodendroglia and to reveal mechanisms of diseases associated with cortical myelin defects.