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

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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.

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Oriol Viader-Llargués

Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, Neuherberg, Germany

Competing interests
The authors declare that no competing interests exist.
Valerio Lupperger

Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany

Competing interests
The authors declare that no competing interests exist.
Laura Pola-Morell

Unit Sensory Biology and Organogenesis, Helmholtz Zentrum München, Neuherberg, Germany

Competing interests
The authors declare that no competing interests exist.
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.
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.

"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.

Copyright

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.