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To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
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Quantitative Analysis of Protein Expression to Study Lineage Specification in Mouse Preimplantation Embryos
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Embryo-scale reverse genetics at single-cell resolution.

Lauren M Saunders1, Sanjay R Srivatsan1, Madeleine Duran1

  • 1Department of Genome Sciences, University of Washington, Seattle, WA, USA.

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|November 15, 2023
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Summary
This summary is machine-generated.

This study presents a comprehensive zebrafish atlas of perturbed embryos, revealing cell type variations and genetic dependencies during development. The data enables new hypotheses on skull development and addresses challenges in developmental genetics.

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Area of Science:

  • Developmental Biology
  • Genomics
  • Cell Biology

Background:

  • Single-cell transcriptomic technologies have advanced cellular atlas generation from whole embryos.
  • Existing atlases often lack data on developmental variation across individual embryos.
  • Understanding latent variation is crucial for a complete picture of development.

Purpose of the Study:

  • To create a comprehensive single-cell transcriptomic atlas of perturbed zebrafish embryos.
  • To analyze developmental variation and genetic dependencies across a large number of individual embryos.
  • To identify novel cell populations and developmental trajectories influenced by genetic perturbations.

Main Methods:

  • Generated single-cell transcriptomic data from 1,812 individually resolved zebrafish embryos.
  • Covered 19 timepoints and 23 genetic perturbations, totaling 3.2 million cells.
  • Employed high replication (≥8 embryos/condition) to estimate variance and detect deviations.

Main Results:

  • Detected perturbation-dependent cell type composition changes relative to wild-type embryos.
  • Resolved developmental trajectories and genetic dependencies in rare cranial ganglia neurons (<1% of embryo).
  • Identified brachyury-independent cells with notochord sheath cell transcriptomes, suggesting new skull development origins.

Conclusions:

  • Standardized, high-resolution, organism-scale single-cell data is key for mapping genetic dependencies in zebrafish.
  • This atlas addresses developmental genetics challenges, including cellular and transcriptional plasticity.
  • The findings provide new hypotheses for early skull development and individual phenotypic diversity.