Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo

Science. 2018 Jun 1;360(6392):981-987. doi: 10.1126/science.aar4362. Epub 2018 Apr 26.

Abstract

High-throughput mapping of cellular differentiation hierarchies from single-cell data promises to empower systematic interrogations of vertebrate development and disease. Here we applied single-cell RNA sequencing to >92,000 cells from zebrafish embryos during the first day of development. Using a graph-based approach, we mapped a cell-state landscape that describes axis patterning, germ layer formation, and organogenesis. We tested how clonally related cells traverse this landscape by developing a transposon-based barcoding approach (TracerSeq) for reconstructing single-cell lineage histories. Clonally related cells were often restricted by the state landscape, including a case in which two independent lineages converge on similar fates. Cell fates remained restricted to this landscape in embryos lacking the chordin gene. We provide web-based resources for further analysis of the single-cell data.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clonal Evolution / genetics*
  • Gene Expression
  • Gene Expression Regulation, Developmental*
  • Glycoproteins / genetics
  • Intercellular Signaling Peptides and Proteins / genetics
  • Sequence Analysis, RNA / methods
  • Single-Cell Analysis / methods
  • Zebrafish / embryology*
  • Zebrafish / genetics*
  • Zebrafish Proteins / genetics*

Substances

  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Zebrafish Proteins
  • chordin