Beyond Adult Stem Cells: Dedifferentiation as a Unifying Mechanism Underlying Regeneration in Invertebrate Deuterostomes.

Cinzia Ferrario,Michela Sugni,Loriano Ballarin,Ildiko M L Somorjai

doi:10.3389/fcell.2020.587320

Abstract

The diversity of regenerative phenomena seen in adult metazoans, as well as their underlying mechanistic bases, are still far from being comprehensively understood. Reviewing both ultrastructural and molecular data, the present work aims to showcase the increasing relevance of invertebrate deuterostomes, i.e., echinoderms, hemichordates, cephalochordates and tunicates, as invaluable models to study cellular aspects of adult regeneration. Our comparative approach suggests a fundamental contribution of local dedifferentiation -rather than mobilization of resident undifferentiated stem cells- as an important cellular mechanism contributing to regeneration in these groups. Thus, elucidating the cellular origins, recruitment and fate of cells, as well as the molecular signals underpinning tissue regrowth in regeneration-competent deuterostomes, will provide the foundation for future research in tackling the relatively limited regenerative abilities of vertebrates, with clear applications in regenerative medicine.

Highlights

Since the time of Aristotle, regeneration has been one of the most fascinating and perplexing biological phenomena to explain, challenging, as it does, the common dogma of irreversibility of ontogenetic processes
Reviewing regeneration with a focus only on the contribution of cell proliferation, blastema formation, or totipotent adult stem cells (ASCs) leaves a large number of unanswered questions on the cellular and molecular underpinnings of this complex process
The impressive variety of regenerative mechanisms displayed within the animal kingdom makes it clear that adopting a comparative approach is as valuable as investigating emerging models

Summary

Introduction

Since the time of Aristotle, regeneration has been one of the most fascinating and perplexing biological phenomena to explain, challenging, as it does, the common dogma of irreversibility of ontogenetic processes. During arm regeneration in Antedon mediterranea, morphologically undifferentiated cells present in the stump tissues (i.e., brachial nerve cortex and coelomic cavities; Figure 2) are recruited to the area where the regenerative blastema will eventually form (Candia Carnevali and Bonasoro, 2001).

Results

Conclusion