PUBLICATION
Whole organism lineage tracing by combinatorial and cumulative genome editing
- Authors
- McKenna, A., Findlay, G.M., Gagnon, J.A., Horwitz, M.S., Schier, A.F., Shendure, J.
- ID
- ZDB-PUB-160528-11
- Date
- 2016
- Source
- Science (New York, N.Y.) 353(6298): aaf7907 (Journal)
- Registered Authors
- Schier, Alexander
- Keywords
- none
- Datasets
- GEO:GSE81713
- MeSH Terms
-
- Animals
- Bacterial Proteins*
- CRISPR-Cas Systems*
- Cell Division/genetics
- Cell Lineage*
- Cell Tracking/methods*
- DNA Barcoding, Taxonomic
- Endonucleases*
- Genetic Engineering/methods*
- Mutation
- Single-Cell Analysis
- Stem Cells/cytology
- Stem Cells/metabolism
- Zebrafish
- Zygote
- PubMed
- 27229144 Full text @ Science
Citation
McKenna, A., Findlay, G.M., Gagnon, J.A., Horwitz, M.S., Schier, A.F., Shendure, J. (2016) Whole organism lineage tracing by combinatorial and cumulative genome editing. Science (New York, N.Y.). 353(6298):aaf7907.
Abstract
Multicellular systems develop from single cells through distinct lineages. However, current lineage tracing approaches scale poorly to whole, complex organisms. Here, we use genome editing to progressively introduce and accumulate diverse mutations in a DNA barcode over multiple rounds of cell division. The barcode, an array of CRISPR/Cas9 target sites, marks cells and enables the elucidation of lineage relationships via the patterns of mutations shared between cells. In cell culture and zebrafish, we show that rates and patterns of editing are tunable and that thousands of lineage-informative barcode alleles can be generated. By sampling hundreds of thousands of cells from individual zebrafish, we find that most cells in adult organs derive from relatively few embryonic progenitors. In future analyses, genome editing of synthetic target arrays for lineage tracing (GESTALT) can be used to generate large-scale maps of cell lineage in multicellular systems for normal development and disease.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping