Biology subjects

Lim, J.

Publications and source records attributed to Lim, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Live Spatial Transcriptomics Enables Longitudinal Tissue Mapping

Spatial transcriptomics has become an important technology in biomedical research by preserving the spatial context of gene expression in tissues and enabling the study of cellular states and interactions in situ. However, most existing methods provide only static snapshots of individual tissue specimens, requiring inference of the molecular dynamics underlying development, disease progression, and therapeutic response from different specimens rather than direct tracking in the same living tissue. Here, we introduce Live Spatial Transcriptomics (Live-ST), a technology that enables longitudinal, transcriptome-wide profiling of living tissue. Live-ST combines electroporation-based intracellular sampling and spatial barcoding to enable repeated, spatially resolved mRNA measurements in intact living tissue through next-generation sequencing. We demonstrate its capabilities by (i) benchmarking spatial mRNA capture in patterned two-dimensional cell systems, (ii) spatially profiling transcriptomes in intact, patient-derived living melanoma tissues while preserving tissue viability, and (iii) longitudinally tracking drug-response dynamics within the tumor microenvironment. Together, Live-ST enables repeated, non-destructive measurements of spatial gene expression, providing a new framework for studying dynamic tissue biology in native physiological and pathological contexts.

bioengineering↗

bioRxiv2026

High-resolution analysis of T cell subsets, clonality, and trajectories in psoriasis

Psoriasis is sustained by type 17 immunity, yet how transcriptionally defined T-cell states are clonally organized across lesions, clinically uninvolved skin, and the circulation remains incompletely understood. We performed paired single-cell RNA and T-cell receptor (TCR) sequencing of T cells isolated from two spatially separated lesions, non-lesional skin, and peripheral blood from 23 participants with psoriasis, together with healthy skin and blood comparators. We resolved 19 cutaneous T-cell populations and found that lesions were enriched for IL-17-associated CD4+ and CD8+ states and activated regulatory T-cell states. CD8+ Tc17 cells showed prominent clonal expansion, and expanded clonotypes contributed more prominently to skin than to blood. Clonotype sharing was greatest between paired lesions, while clonotypes detected in cutaneous IL-17-associated cells mapped to multiple circulating phenotypes, indicating that blood and skin capture complementary features of the disease-associated repertoire. At the sample level, T-cell composition separated 57 lesional samples into two recurrent compositional states that were largely concordant across paired body sites. HLA-C*06:02 status was associated with differences in pretreatment lesional CD8+ T-cell composition, clonotype overlap, and clonal-size distributions. Exploratory longitudinal analyses in eight treated participants showed heterogeneous remodeling of T-cell composition and clonotype detection after therapy. Together, these findings define tissue-restricted and tissue-shared features of the psoriatic T-cell repertoire and identify clonal architecture across skin sites and blood as an organizing feature of lesion heterogeneity.

immunology↗

bioRxiv2026

Erythrocyte aging links hypocalcemia to impaired flow dynamics and oxygen transport through volume dysregulation

Red blood cells (RBCs) maintain their corpuscular volume through mechanotransducive ion-mediated processes in response to circulatory shear stress. However, with age, RBCs accumulate oxidative damage and undergo alterations in protein function, glucose metabolism and ion transport, raising fundamental questions about how volume homeostasis is preserved under mechanical load. Here, we investigated the differential responses of younger (YRBCs) and older RBCs (ORBCs) to fluid shear stress, with a focus on calcium-dependent regulation. We found that ORBCs exhibited a striking dependence on extracellular calcium to maintain volume stability. In calcium-depleted conditions, only ORBCs underwent pronounced post-shear swelling, with recovery only partially restored by ATP-dependent mechanisms. In contrast, calcium preserved volume homeostasis, identifying calcium-sensitive pathways as key compensatory regulators in metabolically compromised ORBCs. Notably, metabolically deficient YRBCs recapitulated the ORBC swelling phenotype, supporting a shift from ATP to calcium-dependent regulation with age. More importantly, shear-induced swelling impaired flow behaviour and oxygen delivery in ORBCs, linking defective volume control to microcirculatory dysfunction. Together, these findings potentially established calcium-dependent volume regulation as a critical adaptive mechanism in ageing RBCs and reveal a previously unrecognized hematological link to vascular dysfunction in hypocalcemia.

bioengineering↗

bioRxiv2026

Synthesis-aware generative design in trillion-scale chemical spaces for automated drug discovery

Autonomous drug discovery via generative molecular design is critically bottlenecked by the production of chemically intractable structures. Multi-trillion-scale make-on-demand libraries guarantee synthetic feasibility, but conventional virtual screening cannot efficiently navigate these vast spaces or address multi-parameter optimization. We introduce Hyper Screening X, a generative AI framework integrating structure-based design with automated synthesis hardware. By encoding deterministic reaction logic in a generative flow network, the framework evaluates only 10 million candidates to navigate an 11-trillion-compound space, jointly optimizing physicochemical properties while ensuring compatibility with automated synthesis. Prospective validation against an SLC1A5 variant with a cryptic interface yielded a 96% synthesis success rate and a 50% functional hit rate, identifying two first-in-class lead compounds. This synthesis-aware strategy advances autonomous, closed-loop drug discovery.

bioinformatics↗

bioRxiv2026

Dual-targeted nanoparticles enable the ex vivo generation of cytotoxic and phagocytic CAR effector cells

Chimeric antigen receptor (CAR)-T cells and CAR-macrophages (or CAR-monocytes) offer complementary antitumor functions. CAR-T cells exert potent cytotoxicity against cancer cells, whereas CAR-macrophages can infiltrate solid tumors, phagocytose cancer cells and promote antigen spreading. Antibody-conjugated lipid nanoparticles (LNPs) have emerged as non-viral mRNA delivery platforms for generating CAR-immune cells. However, these systems have generally been optimized to target a single immune-cell type. Here, to enable the ex vivo generation of CAR-T cells and CAR-monocytes, we developed CLCM08, an anti-CD222 antibody, and co-displayed it with an anti-CD5 antibody on LNPs. CD222 is predominantly expressed by monocytes, macrophages and T cells, and facilitates the internalization of CD222-binding molecules. CD5 is primarily expressed by T cells and has previously been used to enable LNP-mediated mRNA delivery to these cells. Delivery of CAR mRNA by dual CD222/CD5 antibody-conjugated LNPs to primary monocytes and T cells substantially enhanced the ex vivo generation of CAR-monocytes and CAR-T cells compared with non-conjugated LNPs. Moreover, CD19 CAR-T cells and CAR-monocytes generated using dual CD222/CD5 antibody-conjugated LNPs showed enhanced cytotoxic and phagocytic activity, respectively, relative to cells generated using non-conjugated LNPs, with anti-CD222 LNPs producing the largest phagocytic gain in monocytes. These findings establish an adaptable antibody-conjugated LNP-mRNA platform for the ex vivo generation of CAR-T cells and CAR-monocytes.

biochemistry↗

bioRxiv2026

A transcriptomic and spatial map of serotonin autoreceptor expression in Drosophila

Serotonin is an evolutionarily ancient neurotransmitter that modulates an array of behaviors such as mood, sleep, and appetite across species. Serotonin acts primarily by binding to serotonin receptors, which are expressed in post-synaptic neurons (heteroreceptors) and serotonergic neurons themselves (autoreceptors). Serotonin autoreceptors modulate serotonergic tone, the foundational principles of which have been excellently demonstrated in vertebrate and invertebrate models. However, many aspects of the mechanisms and contexts in which this modulation occurs are still unclear. Drosophila melanogaster is a powerful model organism that can provide unique insights into autoreceptor function by the ability to perform precise spatial and temporal genetic manipulation with structural and functional readouts / behaviors of serotonin systems. However, a systematic characterization of serotonin autoreceptor expression in Drosophila has not been conducted. Here we use single-cell sequencing and genetic labeling to show that all five serotonin receptors are expressed in serotonergic neurons and map their expression at both the larval and adult stages of development. This is the first evidence of 5-HT2A and 5-HT7 expression in serotonergic neurons in any organism. Moreover, the unique combinations of autoreceptor expression in specific neuronal clusters will aid in the development of novel hypotheses for autoreceptor function, and demonstrates the utility of Drosophila as a model organism to study the function of serotonin autoreceptors.

neuroscience↗

bioRxiv2026

A Translational Reference for Green Autofluorescence Imaging in the Rhesus Macaque Eye using the OcuMet Beacon

PurposeTo evaluate associations between green autofluorescence (GAF) and structural and functional measures relevant to retinal and optic neuropathies, and to establish normative GAF values across the optic nerve head (ONH), macula, and papillofoveal bundle (PFB) in rhesus macaques. MethodsEighty-two macaques with normal ONH morphology by spectral-domain optical coherence tomography (SD-OCT) were included with a mean {+/-} SD age of 12.76 {+/-} 7.18 (range 0.11-29.39) years. The GAF images were acquired in the ONH, macula and PFB with the OcuMet Beacon. In a subset of macaques (n=19), pattern electroretinogram (PERG) and photopic full-field ERG including the photopic negative response (PhNR) were recorded. ResultsThe GAF significantly increased with age in the ONH, macula and PFB. After adjusting by age, there were no sex differences, but IOP showed a positive association with macular GAF. At the ONH, higher GAF correlated with thinner retinal nerve fiber layer, inner and outer segment complex, and total retinal thickness. In the macula, inner nuclear layer thickness was positively associated with GAF, whereas outer plexiform layer and inner and outer segment complex were inversely associated. The PERG amplitudes inversely tracked ONH GAF. ConclusionsGAF rises with age and IOP, couples to retinal structure, and at the ONH, aligns with inner-retinal functional indices. This study provides a regional reference for GAF in rhesus macaques. Translational RelevanceNormative GAF data in healthy rhesus macaques provide a framework for interpreting this noninvasive signal in translational studies of retinal and optic nerve disease.

physiology↗

bioRxiv2026

Plant functional defects experienced upon growth under Per-/Poly-fluoroalkyl substances (PFAS) conditions

Per- and polyfluoroalkyl substances (PFAS) pose significant environmental risks, yet their impact on food crops like legumes remain insufficiently understood. This study investigated the developmental and physiological responses of hydroponically grown mung bean (Vigna radiata) to varying concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). High concentrations (1 mM) of PFOA severely impaired early plant development, significantly delaying seed germination, reducing leaf emergence, and suppressing root hair formation compared to PFOS and controls. Over a narrower concentration range (5-500 {micro}M), both compounds caused transient growth stunting at early timepoints (48 h), though plants exhibited partial recovery over time. High-dose exposure (500 {micro}M) significantly decreased seedling wet weights, leaf area, and leaf biomass without affecting dry weights, indicating disrupted water retention and homeostasis rather than reduced biomass accumulation. Spectrophotometric analysis revealed a dose- and compound-dependent effect on photosynthesis, with low-dose PFOA (5 {micro}M) significantly increasing leaf chlorophyll absorbance. Furthermore, quantification of callose deposition revealed that high-dose PFOA (500 {micro}M) and medium-dose PFOS (50 {micro}M) raised baseline immune stress responses, which were not further elevated by subsequent flagellin-22 (flg22) challenge, suggesting a contaminant-induced immune priming mechanism. These findings highlight distinct, chemical-specific toxicological impact of PFAS on legume growth, water dynamics, and defence priming, underscoring critical implications for agricultural productivity and food safety.

plant biology↗

bioRxiv2026

Relational Structure Constrains Individual Value Estimates in Visual Working Memory

Reflecting how we organize visual experience in everyday memory, visual working memory is increasingly understood as a system in which individual item representations are organized within structures rather than maintained in isolation. Among these, relational structure may be especially consequential because, by specifying how one item value lies relative to another within a feature space, it could allow information about one remembered value to constrain which values are plausible for the other. Yet demonstrating such constraint is challenging because item-specific mnemonic evidence and relational evidence ordinarily support essentially the same estimate. We broke this equivalence with biased post-encoding feedback for one item, making item-specific and relation-based predictions for the other diverge. Across three experiments, participants remembered two sequentially presented orientations, with feedback for one shifted slightly clockwise or counterclockwise from its actual value. Participants incorporated this bias into memory for the feedback-provided orientation; critically, it also appeared in reports of the other orientation, which received no feedback, in the direction predicted by the signed angular offset linking the two remembered values. This feedback transfer weakened with increasing angular separation but occurred in both directions between the first and second orientations. These findings show that relational structure directly constrains individual value estimates in visual working memory, even for items encountered separately. By dissociating normally coincident item-specific and relation-based predictions, our approach reveals an otherwise hidden relational contribution. A probabilistic account explains these findings through joint inference from uncertain item-specific and relational evidence, with their relative uncertainties governing transfer strength.

neuroscience↗

bioRxiv2026

Ocular Safety and Efficacy of AAV-mediated Tyrosinase Gene Augmentation in a Nonhuman Primate Model

PurposeOculocutaneous albinism type 1 (OCA1) is an inherited disorder caused by tyrosinase (TYR) gene mutations. Affected individuals experience visual impairment and severe photosensitivity from ocular hypomelanosis, with no current treatments. We evaluated the safety and efficacy of a TYR-encoding adeno-associated virus (AAV) vector in healthy rhesus macaques as a potential OCA1 treatment. MethodsA novel AAV2-based capsid (ATX002) was packaged with the human VMD2 promoter and TYR (hTYR) fused with mGreenLantern (mGL). Two adult rhesus macaques were injected with ATX002-hVMD2-hTYR-mGL subretinally (OD) and intravitreally (OS). Safety and efficacy were assessed via comprehensive ophthalmic examination, fundus photography, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography at baseline and defined timepoints up to 12 weeks post-injection, followed by post-mortem immunohistochemistry (IHC). ResultsBoth subretinal doses induced localized hypermelanosis by 3 weeks post-injection, which persisted through the study endpoint and was accompanied by measurable thickening of the retinal pigment epithelium (RPE) on SD-OCT. Histological IHC confirmed successful RPE transduction via robust mGL fluorescence, corroborating in vivo findings by revealing localized RPE hyperplasia and transgene-expressing cells adjacent to regions of de novo hypermelanosis. Intravitreal delivery did not induce any changes to the RPE. Transient uveitis was observed but successfully managed with anti-inflammatory treatment. ConclusionsSubretinal AAV-TYR delivery is a safe and effective approach with the potential to induce RPE pigmentation. These findings support the use of AAV-TYR gene therapy for OCA1, demonstrating efficacy and a manageable safety profile in a large-animal model, and provide a critical bridge toward human clinical translation.

bioengineering↗

bioRxiv2026

Interplay between ferroptosis and guttae in an early-onset murine model of Fuchs endothelial corneal dystrophy (FECD)

Col8a2Q455K/Q455K (Q455K) mice exhibit features of early-onset Fuchs endothelial corneal dystrophy (FECD), including decreased endothelial cell density (ECD) and guttae formation. Within the context of these clinical features, this study longitudinally evaluates ferroptosis in Q455K and wild-type (WT) mice using in vivo imaging, PCR and immunohistochemistry. Fifty-six Q455K and 56 WT mice were evaluated from 3 to 24 months of age with in vivo confocal microscopy; ECD and guttae were measured. Ferroptosis marker expression was determined with PCR and immunohistochemistry (IHC). Data were analyzed using two-way ANOVA with Tukeys post hoc test, Chi-square test and a paired t-test. The ECD significantly decreased in both groups from 3 to 24 months of age, but more markedly in Q455K (2285 {+/-} 317 to 1012 {+/-} 58 cells/mm{superscript 2}) versus WT mice (2714 {+/-} 139 to 2057 {+/-} 149 cells/mm{superscript 2}, P<0.0001). Guttae were observed exclusively in Q455K mice beginning at 3 months of age and increased over time (P=0.0003). The Q455K mice demonstrate guttae at the vertices of corneal endothelial cells rather than their centers (74.3% vs. 25.7%P<0.001). Expression of ferroptosis-related genes (Tfrc, Slc40a1, Ftl1, Gpx4) were significantly increased in the Q455K versus WT mice (P<0.05). Furthermore, corresponding protein expression (transferrin receptor 1, ferroportin, ferritin and glutathione peroxidase 4) was significantly elevated adjacent to guttae in Q455K versus WT mice (P<0.05). These findings implicate guttae in the initiation of ferroptosis as it relates to the pathophysiology of FECD and provide an optimal window for testing novel FECD therapies using this murine model, particularly those that target ferroptosis. Significance StatementFuchs endothelial corneal dystrophy (FECD) is a major cause of corneal blindness, yet the mechanisms driving endothelial cell loss remain unclear. Using an early-onset Q455K murine model, we show that disease onset occurs by 3 months of age and progresses with characteristic corneal guttae, endothelial cell loss, and morphological abnormalities replicating human FECD. By identifying ferroptosis adjacent to guttae in the Q455K, we demonstrate this mechanism is not specific to genetic mutations, but rather a conserved driver of corneal endothelial loss within the context of guttae formation. These findings establish an FECD progression timeline and reveal a mechanistic link between ferroptosis and guttae, validating this model as a critical tool for evaluating targeted therapeutic strategies.

developmental biology↗

bioRxiv2026

BOSE: A Bayesian Order Statistics-Based Estimator for Recovering the Sample Mean and Standard Deviation

In meta-analyses of continuous outcomes, the sample mean and standard deviation (SD) are essential for synthesizing effect sizes across studies. However, clinical studies frequently report alternative summary statistics, such as the median, quartiles, and range. To enable inclusion of such studies, various methods have been proposed to estimate the sample mean and SD from these reported summaries. We propose the Bayesian Order Statistics-based Estimator (BOSE), which leverages the joint likelihood of observed order statistics together with weakly informative priors to obtain the full posterior distribution for the mean and SD without relying on computationally intensive iterative procedures such as Markov chain Monte Carlo algorithms. Our numerical studies demonstrate that BOSE performs competitively with existing approaches in estimating the mean, while achieving superior performance for estimating the SD across all evaluated scenarios, particularly in small-sample settings. Under non-normal distributions including skewed, heavy-tailed, and bimodal settings with mild or moderate deviations from normality, BOSE remains robust and stable, whereas methods specifically designed for skewed distributions may become unstable or even inapplicable. Beyond point estimation, BOSE naturally provides empirically validated posterior credible intervals, enabling researchers to formally quantify uncertainty for study-level estimates and make reliable, evidence-based decisions in meta-analytic research synthesis. A publicly accessible web application implementing BOSE and competing methods is also provided to facilitate practical use in meta-analytic research.

bioinformatics↗

bioRxiv2026

GALE-dependent glycoproteome remodelling is a determinant of oncogenic RAS transformation

Oncogenic transformation is accompanied by extensive remodelling of the cellular glycosylation landscape, yet the mechanisms linking oncogenic signalling to glycoproteome reprogramming remain poorly defined. We used site-resolved intact glycoproteomics to systematically map oncogenic RAS-dependent changes across the N- and O-linked glycoproteome. Integrating multiomics profiling with functional approaches, we identify UDP-glucose 4-epimerase (GALE) as a transcriptional target of oncogenic RAS that is induced through MAPK signalling and MYC-dependent transcription. GALE depletion selectively disrupted RAS-dependent glycoproteome remodelling, preferentially impairing sialylation of N-linked glycans and O-linked GalNAc-type glycosylation. Functionally, these glycosylation defects were accompanied by suppressed anchorage-independent growth and reduced in vivo tumorigenicity of KRAS-mutant cells, establishing GALE-dependent nucleotide-sugar interconversion as a requirement for malignant growth. Clinically, GALE expression was elevated in pancreatic ductal adenocarcinoma, wherein KRAS mutations are highly prevalent, and across a broad spectrum of human cancers. Collectively, our findings define a regulatory axis that connects oncogenic signalling to nucleotide-sugar precursor availability and diversification of the cellular glycan repertoire, revealing GALE as a metabolic dependency in RAS-driven cancer.

Cancer Biology↗

bioRxiv2026

Genetically encoded systems for cytosolic activity recording and molecular archiving across time

Cellular functions are governed by dynamic changes in molecular abundance, state, activity, and interactions within the cytosol. Current molecular tape recorders leverage nuclear transcriptional programs in eukaryotic cells to provide scalable readout of gene regulation dynamics, but cytosolic activity, molecular abundance, and state remain inaccessible. Here, we introduce CyTRACE, a genetically encoded, scalable framework for cytosolic activity recording and molecular archiving across time. CyTRACE ventures beyond the cell nucleus, deploys cytosol-localized protein tape monomers as direct activity sensors and molecule catchers, and offers physiological sensitivity, spatiotemporal resolution, and programmability. Within this modular framework, CytoSense records protease and kinase signaling activities while CytoCatch archives cytosolic proteins, each with temporal continuity in single mammalian cells. CyTRACE thus opens cytosolic biology to scalable activity readout and molecular interrogation.

Synthetic Biology↗

bioRxiv2026

Simultaneous brain-wide single-cell recording resolves spatiotemporal memory architecture

Many fundamental mammalian brain functions emerge from the coordinated activity of cells distributed across large, brain-wide networks. To understand these processes in healthy and diseased states, ideally one would simultaneously measure and analyze single-cell activity at the brain-wide scale, an enduring challenge for live-measurement approaches that often face an inherent tradeoff between spatial resolution and scale. Here, we present GLOBE (sinGle-cell spatiotemporaL recOrding Brain-widE), a technology for brain-wide single-cell recording of cellular activity in vivo with spatiotemporal resolution, physiological sensitivity, and parallelization-accelerated readout. GLOBE leverages genetically encoded intracellular protein tape recorders and a high-throughput computational platform for integrated image and signal analysis. GLOBE records analog signal amplitudes across a continuous time axis, requires only standard light microscopy for in situ readout, and is compatible with expansion microscopy and RNA readouts. We applied GLOBE to simultaneously record transcriptional activity of the immediate early gene Fos in up to 219,703 neurons simultaneously across a single mouse brain over 5.5 continuous days, with a timestamp precision of 3.1-6.7 hours (median absolute error), a local recording density of 69-90% of neurons per imaging field of view, and a post-mortem imaging readout speed of 2.9 seconds per neuron on average. GLOBE resolves the brain-wide spatiotemporal structure of single-cell activity, revealing that Fos transcriptional dynamics associated with fear learning and memory retrieval are distributed across the brain with region-specific temporal heterogeneity, and that the variance of this structure scales down as the number of sampled cells increases. We envision GLOBE to have broad applications for dissecting and decoding physiological and pathological processes at the brain-wide scale.

neuroscience↗

bioRxiv2026

Early Visual Cortex Represents Sensory and Mnemonic Orientations in Separate Subspaces with Preserved Geometry

How early visual cortex (EVC) represents working memory (WM) content while continuing to process incoming sensory input remains unclear. Using fMRI with prolonged delays to isolate mnemonic activity, together with analyses of cross-decoding, low-dimensional subspace structure, and representational geometry, we examined the relationship between sensory and mnemonic orientation representations in human EVC. Cross-decoding generalized poorly between sensory and mnemonic epochs, but this did not imply unrelated codes. Rather, the two occupied separable low-dimensional subspaces while preserving representational geometry across epochs. During discrimination and estimation, sensory- and mnemonic-trained decoders yielded dissociable readouts of concurrent sensory and mnemonic information from the same EVC measurements. Mnemonic coding showed little dependence on the retinotopic radial bias that characterized sensory coding, and trial-by-trial variability in mnemonic representation predicted both discrimination choices and estimation reports. Our findings support a population-level account in which mnemonic information in EVC is re-expressed in a separable but geometrically preserved format.

neuroscience↗

bioRxiv2026

An optimized three-laser 27-color spectral flow cytometry panel for multi-organ profiling in mice

While high-dimensional flow cytometry plays critical roles in resolving complex cellular networks, there remains a scarcity of comprehensive panels for the simultaneous profiling of diverse mouse cell types, primarily due to the inherent difficulty of multiplexing. To address this technical gap and resolve diverse cell populations in murine models, we designed a 27-color flow cytometry panel optimized for 3-laser spectral flow cytometers. This optimized panel enables broad and simultaneous detection of 16 distinct cell subsets from both lymphoid and myeloid lineages--including T cells, B cells, plasma cells, NK cells, innate lymphoid cells, dendritic cells, monocytes, macrophages, neutrophils, eosinophils, basophils, mast cells--along with non-immune cells, such as epithelial, endothelial, fibroblast, and neuronal cells. The panel has been successfully applied to various tissues, including spleen, thymus, bone marrow, peripheral blood, mesenteric lymph nodes, peritoneal lavage fluid, gut epithelium, and lamina propria. Applying this panel to a poly(I:C) model, we successfully tracked dynamic shifts in monocyte and neutrophil populations and identified a previously unrecognized, glucocorticoid-producing cell subset via reporter expression. This panel will facilitate high-dimensional immune profiling on standard 3-laser cytometers, providing a robust tool for dissecting cellular dynamics across diverse contexts.

immunology↗

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↗