Biology subjects

Yun, M. H.

Publications and source records attributed to Yun, M. H..

4 recordsLinked to original sources

bioRxiv2026

Adaptive immunity is dispensable for appendage regeneration in highly regenerative vertebrates

Adaptive immunity has been implicated in tissue repair and homeostasis, however its requirement for complex appendage regeneration in adult vertebrates remains unknown. Here, we show that adaptive immune components are dynamically recruited to regenerating appendages. Using genetic lymphocyte ablation in highly regenerative vertebrates, axolotl (Ambystoma mexicanum) and zebrafish (Danio rerio), we show that mature T and B cells are dispensable for limb, tail and fin regeneration in sexually mature animals. Despite depletion of peripheral and lymphoid T and B populations, Rag1-/- axolotls and zebrafish regenerate appendages with normal kinetics, patterning, and skeletal outcomes. Rag1 -/- regenerating blastemas undergo transcriptomic remodelling including alterations in innate immune and extracellular matrix remodelling genes, accompanied by enhanced neutrophil/myeloid infiltration, highlighting innate immunity as a potential compensatory element for regenerative success. Together, these results indicate that adaptive immunity is not required for restoration of complex appendages in vertebrates, a finding of basic and translational relevance. HighlightsO_LIRag1-/- axolotls lack mature T and B cells in lymphoid organs and periphery. C_LIO_LIRag1-/- axolotls and zebrafish regenerate appendages with kinetics, patterning and sizes comparable to wild-type siblings. C_LIO_LIRag1-/- blastemas show downregulation of adaptive immune programs, modulation of innate immune genes, and heightened myeloid activity and/or infiltration in Rag1-/- animals. C_LIO_LIInnate immune compensation likely enables functional regeneration in the absence of mature adaptive lymphocytes. C_LI

immunology↗

bioRxiv2024

Axolotl epigenetic clocks offer insights into the nature of negligible senescence

Renowned for their regenerative abilities, axolotls also exhibit exceptional longevity, resistance to age-related diseases and apparent lack of physiological declines through lifespan, and have thus been considered organisms of negligible senescence. Whether axolotls display epigenetic hallmarks of ageing remains unknown. Here, we probe the axolotl DNA methylome throughout lifespan and present its first epigenetic clocks. Both at tissue-specific or pan-tissue levels, the clocks are biphasic, capable of predicting age during early life but not for the rest of its lifespan. We show that axolotls exhibit evolutionarily conserved features of epigenetic ageing during early life, yet their methylome is remarkably stable across lifespan, including at Polycomb Repressive Complex 2 (PRC2) target sites, suggesting that this species deviates from known patterns of epigenetic ageing. This study provides molecular insights into negligible senescence and furthers our understanding of ageing dynamics in animals capable of extreme regeneration.

developmental biology↗

bioRxiv2024

The Amphibian Genomics Consortium: advancing genomic and genetic resources for amphibian research and conservation

Amphibians represent a diverse group of tetrapods, marked by deep divergence times between their three systematic orders and families. Studying amphibian biology through the genomics lens increases our understanding of the features of this animal class and that of other terrestrial vertebrates. The need for amphibian genomic resources is more urgent than ever due to the increasing threats to this group. Amphibians are one of the most imperiled taxonomic groups, with approximately 41% of species threatened with extinction due to habitat loss, changes in land use patterns, disease, climate change, and their synergistic effects. Amphibian genomic resources have provided a better understanding of ontogenetic diversity, tissue regeneration, diverse life history and reproductive modes, anti-predator strategies, and resilience and adaptive responses. They also serve as essential models for studying broad genomic traits, such as evolutionary genome expansions and contractions, as they exhibit the widest range of genome sizes among all animal taxa and possess multiple mechanisms of genetic sex determination. Despite these features, genome sequencing of amphibians has significantly lagged behind that of other vertebrates, primarily due to the challenges of assembling their large, repeat-rich genomes and the relative lack of societal support. The emergence of long-read sequencing technologies, combined with advanced molecular and computational techniques that improve scaffolding and reduce computational workloads, is now making it possible to address some of these challenges. To promote and accelerate the production and use of amphibian genomics research through international coordination and collaboration, we launched the Amphibian Genomics Consortium (AGC, https://mvs.unimelb.edu.au/amphibian-genomics-consortium) in early 2023. This burgeoning community already has more than 282 members from 41 countries. The AGC aims to leverage the diverse capabilities of its members to advance genomic resources for amphibians and bridge the implementation gap between biologists, bioinformaticians, and conservation practitioners. Here we evaluate the state of the field of amphibian genomics, highlight previous studies, present challenges to overcome, and call on the research and conservation communities to unite as part of the AGC to enable amphibian genomics research to "leap" to the next level.

genomics↗

bioRxiv2022

Senescent cells enhance newt limb regeneration by promoting muscle dedifferentiation

Salamanders are able to regenerate their entire limbs throughout lifespan, through a process that involves significant modulation of cellular plasticity. Limb regeneration is accompanied by the induction of cellular senescence, a state of irreversible cell cycle arrest associated with profound non-cell-autonomous consequences. While traditionally associated with detrimental physiological effects, here we show that senescent cells enhance newt limb regeneration. Through a lineage tracing approach, we demonstrate that senescent cells promote dedifferentiation of mature muscle tissue to generate regenerative progenitors. In a paradigm of newt myotube dedifferentiation, we uncover that senescent cells promote myotube cell cycle re-entry and reversal of muscle identity via secreted factors. Transcriptomic profiling and loss of function approaches identify the FGF-ERK signalling axis as a critical mediator of senescence-induced muscle plasticity. While chronic senescence constrains muscle regeneration in physiological mammalian contexts, we thus highlight a beneficial role for cellular senescence as an important modulator of dedifferentiation, a key mechanism for regeneration of complex structures.

developmental biology↗