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"
}
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