论文
您当前的位置 :
Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding
论文作者 Xie, LS; Liu, HX; You, ZW; Wang, LY; Li, YW; Zhang, XY; Ji, XS; He, H; Yuan, TL; Zheng, WP; Wu, ZY; Xiong, M; Wei, W; Chen, YJ
期刊/会议名称 NATURE METHODS
论文年度 2023
论文类别 Article; Early Access
摘要 A fundamental interest in developmental neuroscience lies in the ability to map the complete single-cell lineages within the brain. To this end, we developed a CRISPR editing-based lineage-specific tracing (CREST) method for clonal tracing in Cre mice. We then used two complementary strategies based on CREST to map single-cell lineages in developing mouse ventral midbrain (vMB). By applying snapshotting CREST (snapCREST), we constructed a spatiotemporal lineage landscape of developing vMB and identified six progenitor archetypes that could represent the principal clonal fates of individual vMB progenitors and three distinct clonal lineages in the floor plate that specified glutamatergic, dopaminergic or both neurons. We further created pandaCREST (progenitor and derivative associating CREST) to associate the transcriptomes of progenitor cells in vivo with their differentiation potentials. We identified multiple origins of dopaminergic neurons and demonstrated that a transcriptome-defined progenitor type comprises heterogeneous progenitors, each with distinct clonal fates and molecular signatures. Therefore, the CREST method and strategies allow comprehensive single-cell lineage analysis that could offer new insights into the molecular programs underlying neural specification. CREST is a dual-recorder single-cell lineage tracing method for spatiotemporal mapping of the mouse brain.
影响因子 48