BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids
BMP4 patterns Smad activity and generates stereotyped cell fate organization in spinal organoids
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DOI：
10.1242/dev.175430
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发表时间：
2019-07-01
期刊：
影响因子：
4.6
通讯作者：
Ribes, Vanessa C.
中科院分区：
文献类型：
--
作者：
Duval, Nathalie;Vaslin, Celia;Ribes, Vanessa C.
骨形态发生蛋白（BMP）是几种发育组织中细胞命运的分泌调节剂。在胚胎脊髓中，它们控制神经嵴、顶板和背侧中间神经元的不同亚群的出现。尽管已经提出了BMP活性梯度来确定体内细胞类型的身份，但这是否足以在体外形成模式尚不清楚。在这里，我们证明，暴露于BMP 4启动不同的空间动力学的BMP信号在小鼠和人类多能干细胞衍生的脊髓类器官的自发上皮细胞。BMP信号传导的模式导致背神经管细胞类型的定型空间排列，并且BMP 4暴露的浓度、时间和持续时间调节这些模式。此外，小鼠和人类之间的能力时间窗口的持续时间的差异占神经分化的物种特异性克里思。总之，本研究描述了在脊髓类器官中产生背侧中间神经元的模式化子集的有效方法，并支持以下结论：分级BMP活性协调小鼠和人类背侧神经管细胞多样性的空间组织。
Bone morphogenetic proteins (BMPs) are secreted regulators of cell fate in several developing tissues. In the embryonic spinal cord, they control the emergence of the neural crest, roof plate and distinct subsets of dorsal intemeurons. Although a gradient of BMP activity has been proposed to determine cell type identity in vivo, whether this is sufficient for pattern formation in vitro is unclear. Here, we demonstrate that exposure to BMP4 initiates distinct spatial dynamics of BMP signalling within the self-emerging epithelia of both mouse and human pluripotent stem cell-derived spinal organoids. The pattern of BMP signalling results in the stereotyped spatial arrangement of dorsal neural tube cell types, and concentration, timing and duration of BMP4 exposure modulate these patterns. Moreover, differences in the duration of competence time-windows between mouse and human account for the species-specific tempo of neural differentiation. Together, this study describes efficient methods for generating patterned subsets of dorsal intemeurons in spinal organoids and supports the conclusion that graded BMP activity orchestrates the spatial organization of the dorsal neural tube cellular diversity in mouse and human.