生物
神经管
神经上皮细胞
细胞生物学
前脑
类有机物
Hox基因
6号乘客
Wnt信号通路
诱导多能干细胞
SOX2
神经发育
后脑
命运图
神经发生
神经科学
神经干细胞
祖细胞
解剖
胚胎
胚胎干细胞
干细胞
基因表达
遗传学
基因
转录因子
妊娠期
信号转导
怀孕
畸形学
作者
Ashley R.G. Libby,David A Joy,Nicholas Elder,Emily A. Bulger,Martina Z Krakora,Eliza A. Gaylord,Frederico N. Mendoza-Camacho,Jessica C. Butts,Todd C. McDevitt
出处
期刊:Development
[The Company of Biologists]
日期:2021-06-15
卷期号:148 (12)
被引量:40
摘要
Axial elongation of the neural tube is crucial during mammalian embryogenesis for anterior-posterior body axis establishment and subsequent spinal cord development, but these processes cannot be interrogated directly in humans as they occur post-implantation. Here, we report an organoid model of neural tube extension derived from human pluripotent stem cell (hPSC) aggregates that have been caudalized with Wnt agonism, enabling them to recapitulate aspects of the morphological and temporal gene expression patterns of neural tube development. Elongating organoids consist largely of neuroepithelial compartments and contain TBXT+SOX2+ neuro-mesodermal progenitors in addition to PAX6+NES+ neural progenitors. A critical threshold of Wnt agonism stimulated singular axial extensions while maintaining multiple cell lineages, such that organoids displayed regionalized anterior-to-posterior HOX gene expression with hindbrain (HOXB1) regions spatially distinct from brachial (HOXC6) and thoracic (HOXB9) regions. CRISPR interference-mediated silencing of TBXT, a Wnt pathway target, increased neuroepithelial compartmentalization, abrogated HOX expression and disrupted uniaxial elongation. Together, these results demonstrate the potent capacity of caudalized hPSC organoids to undergo axial elongation in a manner that can be used to dissect the cellular organization and patterning decisions that dictate early human nervous system development.
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