A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

We map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and pediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that transformation of early RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting. 1) scRNA-seq of the mouse cerebrum from 11 developmental timepoints - mouse model: Sox2eGFP - # of GFP+ve samples: 11 samples - # of GFP-ve samples: 11 samples. 2) scRNA-seq of mouse cerebral tumours - mouse model: Sox2CreER; P53 f/f; Pten f/+; R26 tdTomato/+ - # of samples: 2 samples.本研究对小鼠大脑在整个发育时间轴（从胚胎第12.5天至出生后第365天）的发育进程进行了全景刻画，对超过10万个细胞实施了单细胞转录组测序。通过将该参考图谱与成人及儿童人脑100余例胶质细胞瘤的单细胞数据进行比对，本研究发现肿瘤细胞的表达特征与受时间调控的胚胎放射状胶质前体细胞（radial glial precursors, RGPs）及其直接亚谱系高度重合。此外，本研究在遗传工程小鼠模型中证实，早期RGPs的恶性转化可形成具备胚胎/幼年RGPs特征的成人脑部肿瘤。综上，上述研究结果表明类胚胎状态的获得是成人胶质瘤发生的关键机制，为阐明人类胶质瘤的起源提供了全新视角，并确定了可用于治疗靶向的特定发育细胞类群。 1. 针对11个发育时间点的小鼠大脑开展单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）：所用小鼠模型为Sox2eGFP；GFP阳性样本量：11例；GFP阴性样本量：11例。 2. 针对小鼠脑部肿瘤开展单细胞RNA测序（scRNA-seq）：所用小鼠模型为Sox2CreER; P53 f/f; Pten f/+; R26 tdTomato/+；样本量：2例。