多区域大脑器官集成大脑,中后脑和内皮系统
Anannya Kshirsagar1, Hayk Mnatsakanyan2, Sai Kulkarni1
1Department for Biotechnology, Advanced Academic Programs, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, 21218, USA.
概括
工程化多区域大脑器官 (MRBOs) 包含多种血管细胞,推进了人类神经发育建模. 这个平台揭示了对大脑发育和疾病研究至关重要的新型内皮神经信号.
科学领域:
- 发育神经科学的发展神经科学.
- 干细胞生物学 干细胞生物学
- 血管生物学 血管生物学
背景情况:
- 目前的大脑器官模型缺乏复杂的内皮细胞多样性,限制了它们对体内人类神经发育的回顾.
- 现有的模型通常依赖于简化的内皮细胞群,阻碍了神经内皮相互作用的研究.
研究的目的:
- 设计先进的多区域大脑器官 (MRBOs),集成多种神经和血管细胞类型.
- 研究复杂内皮细胞群在人类大脑发育和区域模式形成中的作用.
- 确定与神经发育障碍相关的新型内皮神经信号相互作用.
主要方法:
- 顺序调节发育途径以产生独特的神经和内皮细胞器官.
- 优化了融合技术,以整合有机体,同时保持区域身份和细胞融合.
- 单核RNA测序和CellChat分析用于全面的转录和相互作用概况.
主要成果:
- MRBO成功地整合了多种神经和血管细胞类型,包括原生细胞,成熟的内皮细胞,细胞周细胞和脑膜细胞.
- 在人类胎儿大脑组织 (卡内基12-16阶段) 中,MRBO重现了80%的细胞群.
- 确定了13种新的内皮-神经信号交互,其中内皮衍生因素差异性地支持后脑与大脑发育.
结论:
- 通过集成的血管组件,MRBO提供了一个复杂的平台来建模人类大脑发育.
- 这项技术揭示了多样化的内皮细胞在区域大脑模式和神经发育中的关键作用.
- MRBO为研究神经发育障碍提供了强大的工具,其特点是神经内皮细胞信号的破坏.
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