Whole organism lineage tracing by combinatorial and cumulative genome editing. McKenna, A., Findlay, G. M, Gagnon, J. A, Horwitz, M. S, Schier, A. F, & Shendure, J. Science, 26~May, 2016. doi abstract bibtex 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.
@ARTICLE{McKenna2016-dg,
title = "Whole organism lineage tracing by combinatorial and cumulative
genome editing",
author = "McKenna, Aaron and Findlay, Gregory M and Gagnon, James A and
Horwitz, Marshall S and Schier, Alexander F and Shendure, Jay",
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.",
journal = "Science",
pages = "aaf7907",
month = "26~" # may,
year = 2016,
keywords = "
Biotechnology;CRISPR;Development;cancer;classics;evolution;methods;zebrafish;zotero;Zotero
Import (Aug 30);Zotero Import (Aug 30)/My Library;Classics",
language = "en",
issn = "0036-8075, 1095-9203",
doi = "10.1126/science.aaf7907"
}
Downloads: 0
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Here, we use genome editing\n to progressively introduce and accumulate diverse mutations in a\n DNA barcode over multiple rounds of cell division. The barcode,\n an array of CRISPR/Cas9 target sites, marks cells and enables the\n elucidation of lineage relationships via the patterns of\n mutations shared between cells. In cell culture and zebrafish, we\n show that rates and patterns of editing are tunable and that\n thousands of lineage-informative barcode alleles can be\n generated. By sampling hundreds of thousands of cells from\n individual zebrafish, we find that most cells in adult organs\n derive from relatively few embryonic progenitors. 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