瑞典卡罗林斯卡医学院Erik Sundström和Xiaofei Li共同合作,近期取得重要工作进展。他们研究分析了分析人类脊髓发育中的时空基因表达及其对室管膜瘤起源的影响。相关研究成果2023年4月24日在线发表于《自然—神经科学》杂志上。
据介绍,在人类发育中的脊髓中,细胞命运规范的时空调节在很大程度上仍然未知。
通过对单细胞和空间多组学数据进行综合分析,研究人员使用了16个生产前人类样本,在受孕后第5-12周创建了一个全面的脊髓发育细胞图谱。这揭示了神经祖细胞的细胞命运承诺及其空间定位是如何受到特定基因集的时空调控的。研究人员确定了与啮齿类动物相比,人类脊髓发育中的一些独特事件,包括活性神经干细胞的早期静止、细胞分化的差异调节以及细胞命运选择的独特时空遗传调节。
此外,通过将分析图谱与儿科室管膜瘤数据相结合,研究人员确定了进展过程中癌症干细胞的特定分子特征和谱系特异性基因。
因此,这一发育图谱描绘了人类脊髓发育的时空遗传调控,并帮助人们获得对相关疾病见解。
附:英文原文
Title: Profiling spatiotemporal gene expression of the developing human spinal cord and implications for ependymoma origin
Author: Li, Xiaofei, Andrusivova, Zaneta, Czarnewski, Paulo, Langseth, Christoffer Mattsson, Andersson, Alma, Liu, Yang, Gyllborg, Daniel, Braun, Emelie, Larsson, Ludvig, Hu, Lijuan, Alekseenko, Zhanna, Lee, Hower, Avenel, Christophe, Kallner, Helena Kopp, kesson, Elisabet, Adameyko, Igor, Nilsson, Mats, Linnarsson, Sten, Lundeberg, Joakim, Sundstrm, Erik
Issue&Volume: 2023-04-24
Abstract: 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.
DOI: 10.1038/s41593-023-01312-9
Source: https://www.nature.com/articles/s41593-023-01312-9
Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex