研究动态
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分析发育中人类脊髓的时空基因表达模式及其对室管膜瘤来源的启示。

Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin.

发表日期:2023 Apr 24
作者: Xiaofei Li, Zaneta Andrusivova, Paulo Czarnewski, Christoffer Mattsson Langseth, Alma Andersson, Yang Liu, Daniel Gyllborg, Emelie Braun, Ludvig Larsson, Lijuan Hu, Zhanna Alekseenko, Hower Lee, Christophe Avenel, Helena Kopp Kallner, Elisabet Åkesson, Igor Adameyko, Mats Nilsson, Sten Linnarsson, Joakim Lundeberg, Erik Sundström
来源: CLINICAL PHARMACOLOGY & THERAPEUTICS

摘要:

人类发育中的脊髓神经元命运特异性的时空调节仍然大部分未知。本研究通过整合单细胞和空间多组学数据,使用16个人类产前样本,创建了一个全面的发育细胞图谱,覆盖了孕周5-12的脊髓。这揭示了神经前体细胞的命运决策和空间定位如何被特定基因组的时空调节所控制。我们发现人类脊髓发育中的独特事件相对于啮齿类动物,包括较早期的活性神经干细胞静止期、细胞分化的差异调节以及不同的时空遗传调节和细胞命运选择。此外,通过将我们的图谱与小儿脑室管瘤的数据整合,我们确定了癌干细胞在进展过程中的特定分子标志和系谱特定基因。因此,我们勾画了人类脊髓发育的时空遗传调节并利用这些数据来获得疾病洞见。©2023.作者。
The spatiotemporal regulation of cell fate specification in the human developing spinal cord remains largely unknown. In this study, by performing integrated analysis of single-cell and spatial multi-omics data, we used 16 prenatal human samples to create a comprehensive developmental cell atlas of the spinal cord during post-conceptional weeks 5-12. This revealed how the cell fate commitment of neural progenitor cells and their spatial positioning are spatiotemporally regulated by specific gene sets. We identified unique events in human spinal cord development relative to rodents, including earlier quiescence of active neural stem cells, differential regulation of cell differentiation and distinct spatiotemporal genetic regulation of cell fate choices. In addition, by integrating our atlas with pediatric ependymomas data, we identified specific molecular signatures and lineage-specific genes of cancer stem cells during progression. Thus, we delineate spatiotemporal genetic regulation of human spinal cord development and leverage these data to gain disease insight.© 2023. The Author(s).