A robust transcriptional program in newts undergoing multiple events of lens regeneration throughout their lifespan

  1. Konstantinos Sousounis
  2. Feng Qi
  3. Manisha C Yadav
  4. José L Millán
  5. Fubito Toyama
  6. Chikafumi Chiba
  7. Yukiko Eguchi
  8. Goro Eguchi
  9. Panagiotis A Tsonis  Is a corresponding author
  1. University of Dayton, United States
  2. Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, United States
  3. Sanford-Burnham-Prebys Medical Discovery Institute, United States
  4. Utsunomiya University, Japan
  5. Tsukuba University, Japan
  6. National Institutes for Natural Sciences, Japan

Abstract

Newts have the ability to repeatedly regenerate their lens even during ageing. However, it is unclear whether this regeneration reflects an undisturbed genetic activity. To answer this question, we compared the transcriptomes of lenses, irises and tails from aged newts that had undergone 19-times lens regeneration with the equivalent tissues from young newts that had never experienced lens regeneration. Our analysis indicates that repeatedly regenerated lenses showed a robust transcriptional program comparable to young never-regenerated lenses. In contrast, the tail, that was never regenerated, showed gene expression signatures of ageing. Our analysis strongly suggests that, with respect to gene expression, the regenerated lenses have not deviated from a robust transcriptional program even after multiple events of regeneration throughout the life of the newt. In addition, our study provides a new paradigm in biology, and establishes the newt as a key model for the study of regeneration in relation to ageing.

Article and author information

Author details

  1. Konstantinos Sousounis

    Department of Biology, University of Dayton, Dayton, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Feng Qi

    Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Manisha C Yadav

    Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. José L Millán

    Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Fubito Toyama

    Graduate School of Engineering, Utsunomiya University, Utsunomiya, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Chikafumi Chiba

    Faculty of Life and Environmental Sciences, Tsukuba University, Tsukuba, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Yukiko Eguchi

    National Institute for Basic Biology, National Institutes for Natural Sciences, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Goro Eguchi

    National Institute for Basic Biology, National Institutes for Natural Sciences, Okazaki, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Panagiotis A Tsonis

    Department of Biology, University of Dayton, Dayton, United States
    For correspondence
    ptsonis1@udayton.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Alejandro Sánchez Alvarado, Stowers Institute for Medical Research, United States

Ethics

Animal experimentation: Usage of animals complied with the University of Dayton institutional regulations, IACUC protocol ID 011-02. All surgical procedures were performed under anesthesia with 0.1% ethyl 3-aminobenzoate.

Version history

  1. Received: June 21, 2015
  2. Accepted: November 1, 2015
  3. Accepted Manuscript published: November 2, 2015 (version 1)
  4. Version of Record published: December 31, 2015 (version 2)

Copyright

© 2015, Sousounis 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.

Metrics

  • 1,463
    views
  • 371
    downloads
  • 25
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Konstantinos Sousounis
  2. Feng Qi
  3. Manisha C Yadav
  4. José L Millán
  5. Fubito Toyama
  6. Chikafumi Chiba
  7. Yukiko Eguchi
  8. Goro Eguchi
  9. Panagiotis A Tsonis
(2015)
A robust transcriptional program in newts undergoing multiple events of lens regeneration throughout their lifespan
eLife 4:e09594.
https://doi.org/10.7554/eLife.09594

Share this article

https://doi.org/10.7554/eLife.09594

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Junjun Yao, Shaoxing Dai ... Tianqing Li
    Research Article

    While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

    1. Stem Cells and Regenerative Medicine
    Magali Seguret, Patricia Davidson ... Jean-Sébastien Hulot
    Research Article

    We developed a 96-well plate assay which allows fast, reproducible, and high-throughput generation of 3D cardiac rings around a deformable optically transparent hydrogel (polyethylene glycol [PEG]) pillar of known stiffness. Human induced pluripotent stem cell-derived cardiomyocytes, mixed with normal human adult dermal fibroblasts in an optimized 3:1 ratio, self-organized to form ring-shaped cardiac constructs. Immunostaining showed that the fibroblasts form a basal layer in contact with the glass, stabilizing the muscular fiber above. Tissues started contracting around the pillar at D1 and their fractional shortening increased until D7, reaching a plateau at 25±1%, that was maintained up to 14 days. The average stress, calculated from the compaction of the central pillar during contractions, was 1.4±0.4 mN/mm2. The cardiac constructs recapitulated expected inotropic responses to calcium and various drugs (isoproterenol, verapamil) as well as the arrhythmogenic effects of dofetilide. This versatile high-throughput assay allows multiple in situ mechanical and structural readouts.