美国弗吉尼亚大学Eli R. Zunder和Christopher D. Deppmann共同合作，近期取得重要工作进展。他们研究绘制了基于单细胞质谱流式细胞术的发育中小鼠脑图谱。相关研究成果2024年12月18日在线发表于《自然—神经科学》杂志上。

据介绍，哺乳动物大脑的发育需要跨越不同细胞谱系的精确分子变化。虽然发育中大脑中的单细胞RNA丰度已通过单细胞RNA测序（scRNA-seq）进行了表征，但单细胞蛋白质丰度尚未得到表征。

为了弥补这一差距，研究人员对C57/BL6小鼠在胚胎第11.5天（E）至E12.5天的整个大脑，以及在E13.5天至出生后第4天（P4）的端脑、间脑、中脑和菱形脑进行了质谱流式细胞术。使用40个抗体小组分析每个样本两到四个生物重复的24290787个细胞，研究人员从不同的谱系中鉴定出85个分子上不同的细胞簇。

这一分析证实了神经发生和胶质发生的典型分子途径，并预测了皮质少突胶质发生的两种不同轨迹。通过免疫组织化学和RNAscope原位杂交（ISH）验证的，质谱流式细胞术和scRNA-seq中蛋白质与RNA表达的差异，表明了蛋白质水平测量在鉴定功能细胞状态方面的价值。

总之，这一研究结果表明，质谱流式细胞术作为脑组织单细胞分析的可扩展平台是有用的。

附：英文原文

Title: A single-cell mass cytometry-based atlas of the developing mouse brain

Author: Van Deusen, Amy L., Kumar, Sushanth, Calhan, O. Yipkin, Goggin, Sarah M., Shi, Jiachen, Williams, Corey M., Keeler, Austin B., Fread, Kristen I., Gadani, Irene C., Deppmann, Christopher D., Zunder, Eli R.

Issue&Volume: 2024-12-18

Abstract: Development of the mammalian brain requires precise molecular changes across diverse cell lineages. While single-cell RNA abundances in the developing brain have been characterized by single-cell RNA sequencing (scRNA-seq), single-cell protein abundances have not been characterized. To address this gap, we performed mass cytometry on the whole brain at embryonic day (E)11.5–E12.5 and the telencephalon, the diencephalon, the mesencephalon and the rhombencephalon at E13.5–postnatal day (P)4 from C57/BL6 mice. Using a 40-antibody panel to analyze 24,290,787 cells from two to four biological replicates per sample, we identify 85 molecularly distinct cell clusters from distinct lineages. Our analyses confirm canonical molecular pathways of neurogenesis and gliogenesis, and predict two distinct trajectories for cortical oligodendrogenesis. Differences in protein versus RNA expression from mass cytometry and scRNA-seq, validated by immunohistochemistry and RNAscope in situ hybridization (ISH), demonstrate the value of protein-level measurements for identifying functional cell states. Our findings show the utility of mass cytometry as a scalable platform for single-cell profiling of brain tissues.

DOI: 10.1038/s41593-024-01786-1

Source: https://www.nature.com/articles/s41593-024-01786-1