RT Journal Article
SR Electronic
T1 Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain by scGESTALT
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 205534
DO 10.1101/205534
A1 Bushra Raj
A1 Daniel E. Wagner
A1 Aaron McKenna
A1 Shristi Pandey
A1 Allon M. Klein
A1 Jay Shendure
A1 James A. Gagnon
A1 Alexander F. Schier
YR 2017
UL http://biorxiv.org/content/early/2017/10/19/205534.abstract
AB Hundreds of cell types are generated during development, but their lineage relationships are largely elusive. Here we report a technology, scGESTALT, which combines cell type identification by single-cell RNA sequencing with lineage recording by cumulative barcode editing. We sequenced ~60,000 transcriptomes from the juvenile zebrafish brain and identified more than 100 cell types and marker genes. We engineered an inducible system that combines early and late barcode editing and isolated thousands of single-cell transcriptomes and their associated barcodes. The large diversity of edited barcodes and cell types enabled the generation of lineage trees with hundreds of branches. Inspection of lineage trajectories identified restrictions at the level of cell types and brain regions and helped uncover gene expression cascades during differentiation. These results establish scGESTALT as a new and widely applicable tool to simultaneously characterize the molecular identities and lineage histories of thousands of cells during development and disease.