Simultaneous Lineage Tracing and Cell-type Identification Using CRISPR-Cas9-induced Genetic Scars

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2018 Apr 13

PMID 29644996

Citations 236

Authors

Bastiaan Spanjaard

Bo Hu

Nina Mitic

Pedro Olivares-Chauvet

Sharan Janjuha

Nikolay Ninov

Jan Philipp Junker

Affiliations

Soon will be listed here.

Abstract

A key goal of developmental biology is to understand how a single cell is transformed into a full-grown organism comprising many different cell types. Single-cell RNA-sequencing (scRNA-seq) is commonly used to identify cell types in a tissue or organ. However, organizing the resulting taxonomy of cell types into lineage trees to understand the developmental origin of cells remains challenging. Here we present LINNAEUS (lineage tracing by nuclease-activated editing of ubiquitous sequences)-a strategy for simultaneous lineage tracing and transcriptome profiling in thousands of single cells. By combining scRNA-seq with computational analysis of lineage barcodes, generated by genome editing of transgenic reporter genes, we reconstruct developmental lineage trees in zebrafish larvae, and in heart, liver, pancreas, and telencephalon of adult fish. LINNAEUS provides a systematic approach for tracing the origin of novel cell types, or known cell types under different conditions.

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