Simultaneous single-cell profiling of lineages and cell types in the vertebrate brain.

Nat Biotechnol
Authors
Keywords
Abstract

The lineage relationships among the hundreds of cell types generated during development are difficult to reconstruct. A recent method, GESTALT, used CRISPR-Cas9 barcode editing for large-scale lineage tracing, but was restricted to early development and did not identify cell types. Here we present scGESTALT, which combines the lineage recording capabilities of GESTALT with cell-type identification by single-cell RNA sequencing. The method relies on an inducible system that enables barcodes to be edited at multiple time points, capturing lineage information from later stages of development. Sequencing of ∼60,000 transcriptomes from the juvenile zebrafish brain identified >100 cell types and marker genes. Using these data, we generate lineage trees with hundreds of branches that help uncover restrictions at the level of cell types, brain regions, and gene expression cascades during differentiation. scGESTALT can be applied to other multicellular organisms to simultaneously characterize molecular identities and lineage histories of thousands of cells during development and disease.

Year of Publication
2018
Journal
Nat Biotechnol
Volume
36
Issue
5
Pages
442-450
Date Published
2018 06
ISSN
1546-1696
DOI
10.1038/nbt.4103
PubMed ID
29608178
PubMed Central ID
PMC5938111
Links
Grant list
T32 HL007312 / HL / NHLBI NIH HHS / United States
DP1 HD094764 / HD / NICHD NIH HHS / United States
U01 MH105960 / MH / NIMH NIH HHS / United States
R01 HD085905 / HD / NICHD NIH HHS / United States
K99 GM121852 / GM / NIGMS NIH HHS / United States
Wellcome Trust / United Kingdom
T32 GM007266 / GM / NIGMS NIH HHS / United States
DP1 HG007811 / HG / NHGRI NIH HHS / United States