Biology subjects

Joo, S.

Publications and source records attributed to Joo, S..

3 recordsLinked to original sources

bioRxiv2026

A novel fracture lattice in spiny mouse skin facilitates tissue autotomy and regeneration

Autotomy is a unique phenotype whereby an animal sheds a body part to escape predation1-3. The timing and location of autotomy are tightly regulated by preformed planes of weakness (aka fracture planes) which facilitate tissue loss. While autotomy is often followed by regeneration, these phenotypes are rarely reported in mammals4-9. A notable exception are spiny mice (Acomys) which exhibit skin autotomy and more remarkably, complete tissue regeneration10-14. Presently, mechanisms underlying autotomy and complete regeneration in Acomys skin remain elusive. Here, we report the discovery of a honeycomb-like fracture lattice in Acomys skin whose design directs tissue destruction but also facilitates regenerative healing. Unlike the single continuous surface of a fracture plane, this fracture lattice consists of a three-dimensional array of hexagonal units whose boundaries guide tissue breakage. Moreover, we identify collagen VI as the main constituent of the fracture lattice and find that it is distinctly arranged to initiate fracturing and propagation of skin tearing. By preconditioning the tissue for autotomy, the fracture lattice dampens the damage-induced inflammatory response but also upregulates a pro-regenerative gene signature, accelerating skin appendage regeneration. Lastly, we discovered the key role of spiny hairs in fracture lattice formation, as inhibiting their development leads to abnormal pattern formation and changes in skin fracture mechanics. Our results present a novel example of a uniquely evolved structural adaptation in mammalian skin that links tissue patterning, autotomy and regeneration. We expect that the application of a modular compartment structure to artificial skin and other organ engineering may enhance resilience to injury and facilitate efficient regeneration.

developmental biology↗

bioRxiv2022

Influenza infection recruits distinct waves of regulatory T cells to the lung that limit lung resident IgA+ B cells

The role of regulatory T cells (Tregs) in limiting responses to pathogens in tissues remains poorly described. We used scRNA-Seq and a newly generated Foxp3-lineage reporter line (Foxp3-iDTR mice) to track Tregs in the lungs and peripheral blood following infection with influenza virus. Few Tregs of any type were found in the lung at steady-state. Following influenza infection Tregs expressing a strong interferon-stimulated gene signature (ISG-Tregs) appeared by day 3, peaked by day 7, and largely disappeared by day 21 post-infection. A second diverse wave of tissue-repair-like Tregs (TR-Tregs) appeared by day 10 and were maintained through day 21 post-infection. These two distinct Treg subsets had different gene expression patterns and distinct TCR repertoires. To establish the role of Tregs during influenza infection, we acutely ablated Tregs at day 6 post-infection; this resulted in a significant increase in IgA+ B cells in the lung. To determine whether distinct Tregs subsets could also be observed in response to respiratory viral infections in humans we analyzed scRNA-Seq datasets of patients with COVID-19. Peripheral blood from healthy human volunteers had multiple Treg subsets defined by unique gene expression patterns, but few ISG-Tregs. In contrast, two distinct Tregs subsets were expanded in COVID-19 patients - ISG-Tregs and IL32 expressing Tregs (16-fold and 2-fold increased, respectively). ISG-Tregs were present at significantly higher levels in patients with mild versus severe COVID-19, while IL32 expressing Tregs showed the opposite pattern. Thus, the Treg response to respiratory viruses in humans is also diverse and correlates with disease outcome.

immunology↗

bioRxiv2018

Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida

Homeobox transcription factors (TFs) in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, representing remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. To delineate the ancestry of TALE-TALE heterodimerization, we analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization. These results indicate that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution, a likely function being to accurately execute the haploid-to-diploid transitions during sexual development.\n\nAuthor summaryComplex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Highly conserved TALE-superclass homeobox TF networks in major eukaryotic lineages suggest deep ancestry of developmental mechanisms. Our results support the hypothesis that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes, a system that then diversified in the several lineages that engage in complex multicellular organization.

evolutionary biology↗