The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution.

James A Briggs, Caleb Weinreb, Daniel E Wagner, Sean Megason, Leonid Peshkin, Marc W Kirschner, Allon M Klein
Author Information
  1. James A Briggs: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  2. Caleb Weinreb: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  3. Daniel E Wagner: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ORCID
  4. Sean Megason: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ORCID
  5. Leonid Peshkin: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. ORCID
  6. Marc W Kirschner: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. marc@hms.harvard.edu allon_klein@hms.harvard.edu. ORCID
  7. Allon M Klein: Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. marc@hms.harvard.edu allon_klein@hms.harvard.edu. ORCID

Abstract

Time series of single-cell transcriptome measurements can reveal dynamic features of cell differentiation pathways. From measurements of whole frog embryos spanning zygotic genome activation through early organogenesis, we derived a detailed catalog of cell states in vertebrate development and a map of differentiation across all lineages over time. The inferred map recapitulates most if not all developmental relationships and associates new regulators and marker genes with each cell state. We find that many embryonic cell states appear earlier than previously appreciated. We also assess conflicting models of neural crest development. Incorporating a matched time series of zebrafish development from a companion paper, we reveal conserved and divergent features of vertebrate early developmental gene expression programs.

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Grants

  1. T32 GM080177/NIGMS NIH HHS
  2. R01 HD073104/NICHD NIH HHS
  3. K99 GM121852/NIGMS NIH HHS
  4. /Wellcome Trust
  5. R33 CA212697/NCI NIH HHS
  6. R21 HD087723/NICHD NIH HHS

MeSH Term

Animals
Cell Differentiation
Embryonic Development
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Variation
Neural Crest
Neurogenesis
Pluripotent Stem Cells
Sequence Analysis, RNA
Single-Cell Analysis
Transcription Factors
Transcriptome
Xenopus
Zebrafish
Zygote

Chemicals

Transcription Factors