Cellular senescence promotes progenitor cell expansion during axolotl limb regeneration

Developmental Cell, Journal Year: 2023, Volume and Issue: 58(22), P. 2416 - 2427.e7

Published: Oct. 24, 2023

Axolotl limb regeneration is accompanied by the transient induction of cellular senescence within blastema, structure that nucleates regeneration. The precise role this blastemal senescent cell (bSC) population, however, remains unknown. Here, through a combination gain- and loss-of-function assays, we elucidate functions molecular features in vivo. We demonstrate plays positive during axolotl creating pro-proliferative niche supports progenitor expansion blastema outgrowth. Senescent cells impact their microenvironment via Wnt pathway modulation. Further, identify link between signaling propose bSC-derived signals facilitate proliferation neighboring part preventing into senescence. This work defines roles complex structures.

Language: Английский

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The salamander blastema within the broader context of metazoan regeneration

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Aug. 11, 2023

Throughout the animal kingdom regenerative ability varies greatly from species to species, and even tissue within same organism. The sheer diversity of structures mechanisms renders a thorough comparison molecular processes truly daunting. Are “blastemas” found in organisms as distantly related planarians axolotls derived ancestral process, or did they arise convergently independently? Is mouse digit tip blastema orthologous salamander limb blastema? In other fields, characterization reference model has facilitated these comparisons. For example, amphibian Spemann-Mangold organizer served an amazingly useful comparative template field developmental biology, allowing researchers draw analogies between which are superficially quite different. may serve best starting point for analysis regeneration, it been characterized by over 200 years research is supported growing arsenal tools. anatomical evolutionary closeness human also add value translational therapeutic standpoint. Tracing origins blastema, its relatedness throughout kingdom, will both enhance our basic biological understanding regeneration inform selection systems.

Language: Английский

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Multi-species atlas resolves an axolotl limb development and regeneration paradox

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 10, 2023

Humans and other tetrapods are considered to require apical-ectodermal-ridge (AER) cells for limb development, AER-like suggested be re-formed initiate regeneration. Paradoxically, the presence of AER in axolotl, a primary model organism regeneration, remains controversial. Here, by leveraging single-cell transcriptomics-based multi-species atlas, composed human, mouse, chicken, frog cells, we first establish that axolotls contain with characteristics. Further analyses spatial transcriptomics reveal axolotl limbs do not fully re-form during Moreover, mesoderm displays part machinery, revealing program (re)growth. These results clarify debate about extent which developmental is recapitulated

Language: Английский

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Wnt signaling restores evolutionary loss of regenerative potential in Hydra

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

The regenerative potential of animals varies widely, even among closely-related species. In a comparative study regeneration across the Hydra genus, we found that while most species exhibit robust whole-body regeneration, oligactis and other members Oligactis clade consistently fail to regenerate their feet. To investigate mechanisms underlying this deficiency, analyzed transcriptional responses during head foot in H. . Our analysis revealed general injury response lacks activation Wnt signaling, pathway essential for vulgaris regeneration. Notably, transient treatment with agonist triggered foot-specific program, successfully rescuing profiling also dlx2 as likely high-level regulator dependent on signaling activation. establishes framework understanding molecular basis its evolutionary loss

Language: Английский

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Unlocking the Potential of Retinoic Acid: A Comprehensive Review of Its Regulatory Role in Epimorphic Regeneration in Axolotl Limbs for Regenerative Medicine

Regenerative Engineering and Translational Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Language: Английский

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Enduring questions in regenerative biology and the search for answers

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Nov. 9, 2023

Abstract The potential for basic research to uncover the inner workings of regenerative processes and produce meaningful medical therapies has inspired scientists, clinicians, patients hundreds years. Decades studies using a handful highly model organisms have significantly advanced our knowledge key cell types molecular pathways involved in regeneration. However, many questions remain about how unfold regeneration-competent species, they are curtailed non-regenerative organisms, might be induced (or restored) humans. Recent technological advances genomics, biology, computer science, bioengineering, stem hold promise collectively provide new experimental evidence different accomplish process In theory, this should inform design clinical approaches medicine. A deeper understanding tissues organs regenerate will also undoubtedly impact adjacent scientific fields. To best apply adapt these technologies ways that break long-standing barriers answer critical regeneration, we must combine deep developmental evolutionary biologists with hard-earned expertise scientists mechanistic technical end, perspective is based on conversations from workshop organized at Banbury Center, during which diverse cross-section regeneration community experts various discussed enduring biology. Here, share group identified as significant unanswered, i.e., known unknowns. We describe obstacles limiting progress answering expanding number diversity used essential deepening capacity. Finally, propose investigating problems collaboratively across network researchers advance field unexpected insights into important related areas biology

Language: Английский

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Fgf10 mutant newts regenerate normal hindlimbs despite severe developmental defects

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 5, 2024

In amniote limbs, Fibroblast Growth Factor 10 (FGF10) is essential for limb development, but whether this function broadly conserved in tetrapods and/or involved adult regeneration remains unknown. To tackle question, we established Fgf10 mutant lines the newt Pleurodeles waltl which has amazing regenerative ability. While forelimbs develop normally, hindlimbs fail to and downregulate FGF target genes. Despite these developmental defects, mutants were able regenerate normal rather than recapitulating embryonic phenotype. Together, our results demonstrate an important role FGF10 hindlimb formation, little or no regeneration, suggesting that different mechanisms operate during versus development.

Language: Английский

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Nature’s Secret Neuro-Regeneration Pathway in Axolotls, Polychaetes and Planarians for Human Therapeutic Target Pathways

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(22), P. 11904 - 11904

Published: Nov. 6, 2024

Despite significant improvements in the comprehension of neuro-regeneration, restoring nerve injury humans continues to pose a substantial therapeutic difficulty. In peripheral nervous system (PNS), regeneration process after relies on Schwann cells. These cells play crucial role regulating and releasing different extracellular matrix proteins, including laminin fibronectin, which are essential for facilitating regeneration. However, during regeneration, is required regenerate long distance and, subsequently, loses its capacity facilitate this progression. Meanwhile, it has been noted that limited capabilities central (CNS) compared PNS. The CNS contains factors impede axons following axons. presence glial scar formation results from unfavourable condition, where accumulate at site, generating physical chemical barrier hinders neurons. contrast humans, several species, such as axolotls, polychaetes, planarians, possess ability their neural systems amputation. This based vast amount pluripotent stem have remarkable differentiate develop into any cell within body. Although also these cells, numbers extremely limited. Examining molecular pathways exhibited by organisms potential offer foundational understanding human process. review provides concise overview involved axolotl, polychaete, planarian neuro-regeneration. It new perspective approaches neuro-regeneration humans.

Language: Английский

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Post-amputation reactive oxygen species production is necessary for axolotls limb regeneration

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 26, 2022

Introduction: Reactive oxygen species (ROS) represent molecules of great interest in the field regenerative biology since several animal models require their production to promote and favor tissue, organ, appendage regeneration. Recently, it has been shown that ROS such as hydrogen peroxide (H2O2) is required for tail regeneration Ambystoma mexicanum. However, date, unknown whether necessary limb this model. Methods: forelimbs juvenile animals were amputated proximally dynamics was determined using 2'7- dichlorofluorescein diacetate (DCFDA) during process. Inhibition performed NADPH oxidase inhibitor apocynin. Subsequently, a rescue assay exogenous (H2O2). The effect these treatments on size skeletal structures regenerated evaluated by staining with alcian blue alizarin red, well blastema formation, cell proliferation, immune recruitment, expression genes related proximal-distal identity. Results: our results show inhibition post-amputation A. mexicanum salamander model miniature significant reduction elements ulna, radius, overall autopod. Additionally, other effects decrease number carpals, defective joint morphology, failure integrity between structure remaining tissue identified. In addition, treatment affected formation induced levels proliferation structure, CD45+ CD11b + system cells. On hand, blocking proximo-distal identity Aldha1a1, Rarβ, Prod1, Meis1, Hoxa13, Agr2 Yap1 early/mid blastema. Of interest, alterations, rescued application H2O2, suggesting ROS/H2O2 from early stages proper patterning limb.

Language: Английский

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Making a new limb out of old cells: Exploring endogenous cell reprogramming and its role during limb regeneration

AJP Cell Physiology, Journal Year: 2023, Volume and Issue: 326(2), P. C505 - C512

Published: Dec. 18, 2023

Cellular reprogramming is characterized by the induced dedifferentiation of mature cells into a more plastic and potent state. This process can occur through artificial manipulations in laboratory such as nuclear pluripotent stem cell (iPSC) generation, endogenously vivo during amphibian limb regeneration. In amphibians Mexican axolotl, regeneration permissive environment formed nerve-dependent signaling wounded tissue. When exposed to these signals, connective tissue dedifferentiate progenitor-like state allows acquire new pattern information, property called positional plasticity. Here, we review our current understanding endogenous why it important for successful We will also explore how naturally plasticity were leveraged study missing established regenerating

Language: Английский

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