在小鼠大脑中跨基因背景的转录差异的空间单细胞映射
Zachary Hemminger1,2, Gabriela Sanchez-Tam2, Haley De Ocampo2
1Biocartography Inc.
bioRxiv : the preprint server for biology
|October 17, 2024
概括
我们使用集成签名 (ATLAS) 开发了阿特拉斯规模的转录组定位,这是绘制小鼠大脑的新方法. 亚特拉斯揭示了细胞类型和区域组成的显著差异,有助于在疾病模型中进行大脑结构功能分析.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 生物信息学是一种生物信息学.
背景情况:
- 遗传变异会影响大脑的结构和功能.
- 对老鼠大脑的比较分析需要可扩展的,高分辨率的空间转录数据.
- 当前的技术面临的挑战是生成大 atlas 规模的单细胞数据与复制品.
研究的目的:
- 介绍使用聚合签名 (ATLAS) 的Atlas规模转录组定位,这是一个可扩展的组织映射方法.
- 通过基因背景对老鼠大脑进行比较统计分析.
- 促进神经疾病模型的器官层面结构功能分析.
主要方法:
- 亚特拉斯从单细胞RNA测序 (scRNAseq) 数据中学习转录签名.
- 转录签名在现场使用寡核酸探针进行编码.
- 细胞类型和转录组通过解码探针信号来推断.
主要成果:
- 根据MERFISH测量和其他四种技术,ATLAS得到了验证.
- 从C57BL/6J和BTBR小鼠的400多个冠状部分中分析了超过4000万个细胞.
- 在性别和菌株之间发现了40多个细胞类型分布的显著差异和16个区域组成的变化.
结论:
- 亚特拉斯提供了一个可扩展的解决方案,用于生成亚特拉斯规模的空间转录数据.
- 该方法能够对大脑结构和功能进行系统的比较研究.
- 亚特拉斯促进了对大脑中的遗传变异和疾病模型的分析.
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