Live cell-lineage tracing and machine learning reveal patterns of organ regeneration

Abstract

Despite the intrinsically stochastic nature of damage, sensory organs recapitulate normal architecture during repair to maintain function. Here we present a quantitative approach that combines live cell-lineage tracing and multifactorial classification by machine learning to reveal how cell identity and localization are coordinated during organ regeneration. We use the superficial neuromasts in larval zebrafish, which contain three cell classes organized in radial symmetry and a single planar-polarity axis. Visualization of cell-fate transitions at high temporal resolution shows that neuromasts regenerate isotropically to recover geometric order, proportions and polarity with exceptional accuracy. We identify mediolateral position within the growing tissue as the best predictor of cell-fate acquisition. We propose a self-regulatory mechanism that guides the regenerative process to identical outcome with minimal extrinsic information. The integrated approach that we have developed is simple and broadly applicable, and should help define predictive signatures of cellular behavior during the construction of complex tissues.

Article and author information

Author details

  1. Oriol Viader-Llargués

    Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Valerio Lupperger

    Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Laura Pola-Morell

    Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Carsten Marr

    Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany
    For correspondence
    carsten.marr@helmholtz-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
  5. Hernán López-Schier

    Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, Neuherberg, Germany
    For correspondence
    hernan.lopez-schier@helmholtz-muenchen.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7925-7439

Funding

European Research Council (2007_205095)

  • Hernán López-Schier

AGAUR (2009-SGR-305)

  • Hernán López-Schier

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Zebrafish were maintained under standard conditions. Experiments with wild-type, mutant and transgenic embryos of undetermined sex were conducted in accordance with institutional guidelines and under a protocol approved by the Ethical Committee of Animal Experimentation of the Parc de Recerca Biomedica de Barcelona, Spain, and protocol number Gz.:55.2-1-54-2532-202-2014 by the "Regierung von Oberbayern", Germany.

Reviewing Editor

  1. Tanya T. Whitfield, University of Sheffield, United Kingdom

Publication history

  1. Received: July 27, 2017
  2. Accepted: March 28, 2018
  3. Accepted Manuscript published: March 29, 2018 (version 1)
  4. Version of Record published: April 17, 2018 (version 2)
  5. Version of Record updated: April 18, 2018 (version 3)

Copyright

© 2018, Viader-Llargués et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Oriol Viader-Llargués
  2. Valerio Lupperger
  3. Laura Pola-Morell
  4. Carsten Marr
  5. Hernán López-Schier
(2018)
Live cell-lineage tracing and machine learning reveal patterns of organ regeneration
eLife 7:e30823.
https://doi.org/10.7554/eLife.30823

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