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Gastrulation01:56

Gastrulation

Gastrulation establishes the three primary tissues of an embryo: the ectoderm, mesoderm, and endoderm. This developmental process relies on a series of intricate cellular movements, which in humans transforms a flat, “bilaminar disc” composed of two cell sheets into a three-tiered structure. In the resulting embryo, the endoderm serves as the bottom layer, and stacked directly above it is the intermediate mesoderm, and then the uppermost ectoderm. Respectively, these tissue strata will form...

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Mapping lineage-traced cells across time points with moslin.

Marius Lange1,2,3, Zoe Piran4, Michal Klein5

  • 1Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

Genome Biology
|October 21, 2024
PubMed
Summary

This study introduces moslin, a new computational model that integrates gene expression and lineage tracing to predict cell fates. It enhances understanding of cellular decision-making in development and regeneration.

Keywords:
Cellular dynamicsFate decisionsLineage tracingOptimal transportRegeneration

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Area of Science:

  • Computational Biology
  • Developmental Biology
  • Systems Biology

Background:

  • Simultaneous single-cell gene expression and lineage history profiling is crucial for understanding cellular decision-making.
  • Existing computational methods for trajectory inference often fail to utilize all lineage information from time-series experiments.

Purpose of the Study:

  • To develop a novel computational model, moslin, for integrating gene expression and lineage information across time points.
  • To predict cell fate probabilities and identify key genes driving cellular decisions.
  • To apply the model to diverse biological systems, including embryonic development and tissue regeneration.

Main Methods:

  • Developed moslin, a Gromov-Wasserstein-based model to couple cellular profiles across time points.
  • Utilized lineage and gene expression data for model training and validation.
  • Applied the model to simulated data, Caenorhabditis elegans embryonic development, and zebrafish heart regeneration.

Main Results:

  • moslin successfully integrates gene expression and lineage information to create coupled cellular profiles.
  • Validated the model's ability to predict cell fate probabilities in simulations and experimental data.
  • Identified putative gene drivers of cellular decisions during Caenorhabditis elegans development.
  • Delineated lineage relationships among transient fibroblast states during zebrafish heart regeneration.

Conclusions:

  • moslin offers a powerful new approach for analyzing multi-modal single-cell data in time-series experiments.
  • The model advances the study of cellular decision-making processes in both development and regeneration.
  • This work provides a framework for deeper insights into complex biological systems through integrated data analysis.