Biology subjects

Abe, T.

Publications and source records attributed to Abe, T..

At least 19 recordsLinked to original sources

bioRxiv2026

Ductal myofibroblasts reactivate contractile program to stabilize alveolar architecture during lung regeneration

The alveolar sac architecture is essential for efficient gas exchange and must be precisely maintained throughout life; however, how this delicate structure is preserved during adult regeneration remains poorly understood. Using a mouse pneumonectomy model, we found that Lgr6+ Hhip+ ductal myofibroblasts, a poorly characterized mesenchymal population, are indispensable for maintaining alveolar integrity during lung regrowth. Comprehensive characterization using single-cell transcriptomics, mouse genetics, and pharmacological assays demonstrated that these ductal myofibroblasts secrete myogenic factors, most notably CCN4, to reactivate a myogenic program that converts them into contractile PA-DMFs, thereby preserving alveolar architecture. Lineage-tracing further revealed that these ductal myofibroblasts originate from embryonic MCAM- SMA+ distal progenitors via subepithelial TGF-{beta} signaling, serving as a lifelong guardian of alveolar structural integrity. Notably, cross-species analysis identified an analogous population of LGR6+ fibromyocytes in human respiratory bronchioles. Together, these findings indicate ductal myofibroblasts as a developmentally programmed cell population that reactivate a contractile program to structurally support the regeneration of adult lungs.

developmental biology↗

bioRxiv2026

Hypothermic Conditions Impair GnRH Pulse Generator Activity and Gametogenesis

Mammalian reproductive function is driven by arcuate kisspeptin neurons, pacemakers of gonadotropin secretion. During energy shortages, animals reallocate resources from reproduction to survival; however, the underlying neural mechanisms remain elusive. Here we used fiber photometry to chronically monitor synchronized episodes of arcuate kisspeptin neuron activity (SEskiss) in adult mice under various energy-saving conditions. In both sexes, SEskiss frequency was markedly suppressed during fasting-induced torpor and pharmacologically induced hypothermia, whereas hypometabolism alone had no discernible effect. A Q neuron-induced hypothermic state (QIH) robustly suppressed SEskiss, leading to impaired gamete maturation, whereas warming the body temperature during QIH fully restored SEskiss frequency. These findings demonstrate that hypothermia, rather than hypometabolism, is the primary driver of suppression of the hypothalamic reproductive axis during energy-saving conditions. This study provides insights into how thermal signals act as critical gatekeepers in the mammalian reproductive system.

neuroscience↗

bioRxiv2026

Genome editing of marsupial RSX reveals conserved and divergent principles in mammalian X-inactivation

X-chromosome inactivation balances X-gene dosage between the sexes in eutherians and marsupials. The lncRNA Xist mediates X-inactivation in eutherians but is absent from marsupials. An evolutionarily unrelated lncRNA, RSX, has been identified in marsupials, but its role in X-inactivation is unresolved because genome editing in these mammals has only recently become feasible. Using CRISPR-Cas9 in the opossum, we show that RSX is required for the initiation of X-inactivation in marsupial embryos. RSX deletion later, in differentiated cells, causes modest X-gene de-repression, with repressive chromatin marks H3K27me3 and H3K9me3 retained. H2AK119ub is not enriched on the opossum inactive X, revealing divergent Polycomb-mediated regulation in therians. Our findings reveal stage-specific roles of RSX in marsupial X-inactivation and identify conserved and divergent features of X-dosage compensation in mammals.

genomics↗

bioRxiv2026

Circulating miR-1285-3p promotes age-associated B cell differentiation through the OXPHOS-IKZF2 axis in SLE

Age-associated B cells (ABCs) expand in systemic lupus erythematosus (SLE) and contribute to pathogenic humoral immunity, but the mechanisms that restrain their differentiation remain unclear. Here, we identify the transcription factor IKZF2 (Helios) as a regulator that limits ABC differentiation. Transcriptomic and functional analyses showed that suppression of oxidative phosphorylation (OXPHOS) in B cells promoted ABC differentiation and was accompanied by reduced IKZF2 expression. Pharmacologic modulation of mitochondrial metabolism further demonstrated that OXPHOS inhibition promoted, whereas OXPHOS activation restrained, ABC differentiation. Integrative analyses revealed reduced IKZF2 expression in selected B cell subsets from patients with SLE. Functional suppression of IKZF2 enhanced ABC differentiation and attenuated the inhibitory effects of OXPHOS activation, indicating that IKZF2 mediates metabolic control of B cell fate. Mechanistically, IKZF2 restrained early ABC-associated gene programs, including ITGAX and TBX21. Circulating miR-1285-3p in small extracellular vesicles, elevated in SLE, suppressed OXPHOS and recapitulated these effects. Together, these findings identify an OXPHOS-IKZF2 axis that restrains pathogenic B cell differentiation and links extracellular microRNA-mediated metabolic stress to ABC formation in SLE. One-sentence summarySmall EV-associated miR-1285-3p in SLE promotes ABC differentiation by suppressing OXPHOS and relieving IKZF2-mediated restraint.

immunology↗

bioRxiv2026

Plagl2 unlocks the latent regenerative potential of Müller glia in the adult mouse retina

Muller glia (MG) in the adult mammalian retina have long been recognized as a potential endogenous source for the regeneration of lost retinal neurons. However, existing MG reprogramming strategies yield an incomplete regenerative response by favoring either proliferation or neurogenic differentiation. Here, we show that the zinc-finger transcription factor Plagl2, which has been demonstrated to rejuvenate aged neural stem cells, was sufficient to reprogram adult mouse MG into a progenitor-like state with coupled proliferative and neurogenic competence. Using histology, time-lapse imaging, and single-cell transcriptomics, we found that Plagl2 drove regulated rounds of MG cell cycle re-entry, while N-methyl-D-aspartate-induced retinal injury further promoted the acquisition of neurogenic competence toward inner nuclear layer neuronal identities. These findings identify Plagl2 as a novel rejuvenator of mammalian MG and support the general principle that reprogramming modules can be redeployed across cell types, offering new avenues for unlocking regenerative potential in otherwise non-regenerative tissues.

neuroscience↗

bioRxiv2026

E3 ubiquitin ligase HUWE1 mediates K6-linked polyubiquitylation and stabilization of Nrf2 in an HBx-dependent manner, thereby inhibit ing hepatitis B virus replication

Hepatitis B virus (HBV) infection remains a major global health burden, and HBV X protein (HBx) plays a central role in modulating host pathways that influence viral replication. We previously reported that the oxidative stress sensor Kelch-like ECH-associated protein 1 (Keap1) recognizes HBx to activate the NF-E2-related factor 2 (Nrf2) signaling pathway to suppress HBV replication. Although canonical K48-linked ubiquitylation is known to control Nrf2 turnover, the contribution of non-canonical ubiquitin linkages to Nrf2 regulation during HBV infection remains unclear. Here, we investigated the role of HECT, UBA, and WWE domain-containing E3 ubiquitin ligase 1 (HUWE1) in the regulation of Nrf2 in the context of HBV replication. Cell-based ubiquitylation assays demonstrated that HUWE1 knockdown reduced HBx-mediated K6-linked polyubiquitylation of Nrf2, while overexpression of wild-type HUWE1, but not the catalytically inactive HUWE1(C4341A) mutant, enhanced it. Coimmunoprecipitation and proximity ligation assays demonstrated that HUWE1 interacts with HBx in the cytoplasm and binds Nrf2 only in the presence of HBx, suggesting that HBx promotes the interaction between HUWE1 and Nrf2. Cycloheximide chase assays demonstrated that HUWE1 knockdown destabilized Nrf2 in HBx-expressing cells. Furthermore, depletion or pharmacological inhibition of HUWE1 increased intracellular HBV RNA and pgRNA levels as well as extracellular HBV DNA and HBsAg levels in HBV-infected cells. Collectively, these results support a model in which HUWE1 mediates HBx-dependent K6-linked polyubiquitylation and stabilization of Nrf2 to restrict HBV replication. This study expands current understanding of non-canonical ubiquitin signaling in HBV-host interactions. DATA SUMMARYAll data are presented in the main figures. The data that support the findings of this study is available at bioRxiv (https://doi.org/10.64898/2026.04.20.719611). Raw sequencing data, microscopy images, materials, and sequence information are available upon request. Correspondence and requests for materials should be addressed to Professor Ikuo Shoji. IMPACT STATEMENTHepatitis B virus (HBV) chronically infects approximately 254 million people worldwide, yet host mechanisms that restrict viral replication remain incompletely understood. The Keap1/ Nrf2 signaling pathway is a central defense against oxidative stress. Under basal conditions, Nrf2 is targeted for degradation via Keap1/Cullin3-mediated K48-linked polyubiquitylation. Here, we provide evidence that the E3 ubiquitin ligase HUWE1 contributes to HBx-dependent K6-linked polyubiquitylation and stabilization of Nrf2. Our findings support a model in which non-canonical ubiquitin signaling helps shape the HBV-host interactions and contributes to suppression of viral replication. This study extends current understanding of the ubiquitin code in HBV infection and highlights HUWE1 as a candidate component of an anti-HBV regulatory pathway.

microbiology↗

bioRxiv2026

R-spondin 1 restores hypothalamic glucose-sensing and systemic glucose homeostasis via Wnt signaling in diet-induced obese mice

High-fat diet (HFD) feeding disrupts systemic glucose metabolism, yet the underlying neural mechanisms remain incompletely understood. Here, we demonstrate that glucose-excited (GE) neurons in the ventromedial hypothalamus (VMHGE) are essential for acute glucose regulation and that their function is compromised by HFD via structural synaptic remodeling. We found that HFD feeding suppresses canonical Wnt signaling and downregulates R-spondin 1 (RSPO1), a Wnt enhancer, in the VMH. This Wnt inhibition leads to a loss of dendritic spines and blunted glucose-sensing in VMHGE neurons. Conversely, central administration of RSPO1 restores Wnt/{beta}-catenin signaling, promotes synaptogenesis, and recovers neuronal glucose responsiveness. Consequently, RSPO1 treatment ameliorates HFD-induced glucose intolerance by enhancing peripheral glucose utilization. These findings identify the RSPO1-Wnt signaling axis as a critical regulator of VMH neuronal plasticity and metabolic homeostasis, providing a mechanistic link between diet-induced synaptic pathology and systemic metabolic dysfunction. Highlights- Glucose-excited neurons in VMH were labeled with TRAP - VMH glucose-excited neurons regulates systemic glucose metabolism - Wnt signaling regulates synaptogenesis in VMH and maintain neuronal glucose-sensitivity - R-spondin1 recovers VMH neuronal glucose sensitivity in HFD fed obese mice

neuroscience↗

bioRxiv2026

Ribonuclease L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA

During viral infection, viral replication perturbs endoplasmic reticulum (ER) homeostasis and triggers the unfolded protein response (UPR). XBP1s, a transcription factor generated by one branch of the UPR, is known to potentiate both innate and adaptive immunity, but its role in antiviral responses remains incompletely understood beyond its ability to augment type I interferon (IFN) mRNA induction. Here, we show that XBP1s positively regulates the RIG-I-like receptors (RLRs), ribonuclease L (RNase L), and protein kinase R (PKR) pathways, indicating that it enhances all three major antiviral response pathways. We further show that RNase L activation rapidly decreases XBP1 mRNA levels in an RNase activity-dependent manner, leading to a prompt reduction in XBP1s expression. Consistent with this, RNase L deletion significantly increased both thapsigargin-mediated XBP1s induction and XBP1s expression following Japan encephalitis virus infection. Poly(I:C)-induced IFNB mRNA expression was significantly enhanced in RNase L-knockout cells. This enhancement was completely abolished by RNase L reconstitution. XBP1 knockdown also significantly attenuated IFNB mRNA expression in RNase L-knockout cells. These findings suggest a negative-feedback loop in which RNase L suppresses XBP1s, thereby fine-tuning antiviral responsiveness during viral infection. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/713401v1_ufig1.gif" ALT="Figure 1000"> View larger version (19K): org.highwire.dtl.DTLVardef@112d312org.highwire.dtl.DTLVardef@df79a9org.highwire.dtl.DTLVardef@1ac571borg.highwire.dtl.DTLVardef@18ac610_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2026

Co-targeting an AMPK--MAPK axis reprograms CAFs and suppresses PDAC

Pancreatic ductal adenocarcinoma (PDAC) is a fatal cancer characterized by limited therapeutic options and a highly treatment-resistant tumor microenvironment. Beyond tumor-intrinsic genetic alterations, growing evidence indicates that host-microbiome interactions influence cancer progression through microbial metabolites. However, how microbiome-derived metabolites influence oncogenic signaling in PDAC remains unclear. Here, integrated profiling revealed a consistent reduction of the microbial metabolite acetic acid in fecal samples from treatment-naive patients with PDAC and in a genetically defined Drosophila model recapitulating key PDAC driver alterations. Acetic acid activates AMP-activated protein kinase, and pharmacological activation of this pathway together with inhibition of mitogen-activated protein kinase signaling suppressed tumor growth in fly and mouse models. Combined pathway targeting restored AMPK activity and suppressed cancer-associated fibroblast activation. These findings identify a microbiome-associated metabolic vulnerability in PDAC and suggest that coordinated targeting of metabolic and oncogenic signaling may restrain tumor progression and improve therapeutic strategies.

cancer biology↗

bioRxiv2026

Unsupervised explainable AI reveals similar oligonucleotide-usage zones matching the highest-resolution human chromosome bands

Unsupervised and explainable AI can uncover genomic features that extend beyond human expectations. Oligonucleotides such as penta- and hexanucleotides often function as core binding motifs for regulatory proteins, and their usage provides a powerful tool in functional genomics. We applied an unsupervised, explainable AI approach to odds ratio (observed/expected) profiles of all 1-Mb euchromatic fragments in the human genome. This odds-ratio analysis identified oligonucleotide features independent of mononucleotide composition, thereby highlighting functional roles of oligonucleotide motifs. AI-based clustering of all 1-Mb euchromatic fragments, using either penta- or hexanucleotide odds ratios (1,024 or 4,096 variables), unexpectedly revealed nearly 2,000 distinct zones, despite the large differences in dimensionality. If these [~]2,000 zones represent biologically meaningful segmentations, comparable structures would be expected to emerge when other oligonucleotide types are analyzed. Consistent with this expectation, CG-containing penta- and hexanucleotides (244 and 1,185 variables) produced comparable [~]2,000 zones, indicating that the underlying segmental structures reflect fundamental functional divisions within the genome. Human chromosomes exhibit well-established Giemsa-banding patterns comprising 850 bands at prometaphase and 2,000 bands at prophase. Since single-nucleotide coordinates are available for the 850 bands, we identified a diagnostic oligonucleotide set that distinguishes Giemsa-negative and -positive regions. Computational pseudo-band reconstruction based on this set generated genome segmentations that more closely paralleled the AI-derived [~]2,000 clusters than the 850 bands. These unexpected findings indicate that AI captures the characteristic features of chromosomal bands and can predict high-resolution banding from genome sequences alone, thereby bridging classical cytogenetics and modern AI-based genomics.

genomics↗

bioRxiv2026

Rice Jumonji706 confers the photoperiod sensitivity in rice by distinct regulation of short-day and long-day flowering time regulatory pathways.

Photoperiod sensitivity (PS) is a key biological response in plants as they adapt to specific environments. Rice (Oryza sativa L.) exhibits a clear PS, as it implements critical phase transition decisions based on PS signals. In this study, we identified a novel PS gene, JMJ706, that is expected to deliver photoperiod-related signals to the flowering-time regulatory network in a day-length-dependent manner. The JMJ706 mutants exhibit early flowering under LD and later flowering under SD compared to WT plants. The gene encodes an H3K9me2 demethylase, and under long-day (LD) conditions, its demethylase activity facilitates the expression of Grain number, Plant height, and Heading-date7 (Ghd7). Since Ghd7 is a floral repressor in LD, it promotes the vegetative phase by delaying flowering. Under short-day conditions (SD), H3K9me2 demethylase activity facilitates Early heading-date 1 (Ehd1) expression, and it acts as a floral accelerator by inducing Heading date 3 (Hd3a) and RICE FLOWERING LOCUS T 1 (RFT1). Furthermore, we propose that the daylength-dependent promotion of target genes (Ghd7 and Ehd1) occurs through demethylation of specific promoter regions at a crucial time window. In addition, JMJ706 may play an important role in regulating plant architecture, including plant height. The natural variation in JMJ706 alleles shows high frequencies across major rice subpopulations, suggesting that JMJ706 could play an important role in the geographical distribution and adaptation of rice cultivars. Our results may add a new layer to the rice flowering-time regulatory pathway, supporting regional adaptation and potential for future breeding.

plant biology↗

bioRxiv2026

Microgravity affects the nervous system and aging in C. elegans through reduced tactile stimulation

Space travel is becoming accessible, yet our understanding of how space environment and microgravity ({micro}G) affect biology, physiology, and health remains incomplete. We investigated {micro}G effects on neuromuscular development and aging in Caenorhabditis elegans. Nematodes in {micro}G showed downregulation of genes related to synaptic signaling, dopamine response, locomotion, and cuticle development, with impaired synaptic vesicle dynamics, reduced motility, and shorter body lengths. Aged worms in {micro}G showed decreased collagen gene expression, increased motor neuron defects, synaptic vesicle accumulation and decreased release, and mitochondrial morphology collapse in body wall muscles, indicating accelerated aging. MEC-4 mechanoreceptor was identified as a key mediator of {micro}G-induced body length reduction and changes in extracellular matrix gene expression. {micro}G conditions suppressed mechanoreceptor genes, suggesting multiple mechanosensory systems are affected. Physical stimulation through culture medium with small beads in space mitigated many {micro}G-induced expression changes, including mechanoreceptors, neuromuscular defects, and aging-related phenotypes. These results highlight mechanical stimulis role in maintaining neuromuscular integrity during spaceflight and suggest restoring tactile input could counter health risks from reduced stimulation in long-term space missions. SIGNIFICACEWe found that microgravity ({micro}G) conditions suppress the expression of multiple mechanoreceptor genes in Caenorhabditis elegans, indicating that several mechanosensory systems are affected during spaceflight. Importantly, reintroducing physical stimulation by adding small beads to the culture medium in space partially reversed many of these {micro}G-induced gene expression changes. This intervention also mitigated neuromuscular defects and aging-related phenotypes observed under {micro}G conditions. Collectively, these findings underscore the essential role of mechanical stimuli in preserving neuromuscular integrity during space missions and suggest that restoring tactile input may be a promising strategy to counteract the health risks associated with reduced tactile stimulation during prolonged spaceflights.

systems biology↗

bioRxiv2025

HDA19-mediated deacetylation of histone H3.3 lysine 27 and 36 regulates plant sensitivity to salt stress

Plants survive extreme environments through rapid chromatin reprogramming, yet the epigenetic marks that confer stress resilience remain poorly understood. Histone deacetylase HDA19 is a key epigenetic regulator in Arabidopsis, and hda19-deficient mutants display tolerance to multiple abiotic stresses, including drought, heat, and salinity. Using lysine acetylome profiling, we identified a non-canonical K27/K36 di-acetylation mark on histone H3.3, among nine H3 variants, as a specific substrate of HDA19. Under salinity stress, this mark decreased in wild-type plants but increased in hda19 mutants, while other known H3 modifications were similarly affected in both genotypes. Mimicking constitutive di-acetylation of H3.3 K27/K36 through lysine-to-glutamine substitutions promoted accumulation of stress-responsive late embryogenesis abundant (LEA) proteins and conferred salinity tolerance in seedlings, phenocopying hda19 mutants. Furthermore, generating the lea7-1/lea29-1/rab18-1 triple mutant abolished hda19-dependent salinity tolerance, confirming the LEA proteins role downstream of HDA19. Our findings demonstrate that H3.3 K27/K36 di-acetylation, modulated by HDA19, drives LEA protein accumulation and enables plants to withstand environmental stress, revealing a previously unknown core mechanism of plant stress resilience. Significance statementHistone acetylation is crucial for regulating chromatin states and transcription, yet the specific histone codes controlled by histone deacetylases and acetyltransferases during plant stress acclimation remain unclear. Arabidopsis mutants lacking histone deacetylase 19 show enhanced tolerance to drought, heat, and salinity. Using acetylome profiling and genetic analyses, we identify a previously unknown di-acetylation of histone H3.3 at lysines 27 and 36 as a key epigenetic switch activating late embryogenesis abundant proteins essential for salt tolerance in seedlings. This discovery reveals a novel mechanism linking histone H3.3 K27/K36 di-acetylation to stress-resilient protein accumulation, offering new insights into epigenetic control of plant stress responses and informing strategies to improve crop resilience under climate change.

plant biology↗

bioRxiv2025

Submedius Thalamus Modulates Orbitofrontal Cortex Representations During Maternal Behavior in Mice

The orbitofrontal cortex (OFC) is central to cognitive and social functions, yet its presynaptic partners remain incompletely defined. In female mice, the OFC modulates infant-directed maternal caregiving behaviors essential for offspring survival in an experience-dependent manner. Here, we identify the submedius thalamus (SMT) as a major presynaptic partner of the OFC. Trans-synaptic tracing revealed intensive inputs from both the SMT and mediodorsal thalamus (MD) to OFC layer 5 excitatory neurons. A mouse line Tnnt1-Cre enabled selective targeting of these higher-order thalamic nuclei. Axonal tracing demonstrated complementary projection patterns of SMT and MD across prefrontal regions. Microendoscopic Ca2+ imaging demonstrated pup retrieval encoding in SMT and MD, but only SMT exhibited learning-related plasticity, characterized by enhanced anticipatory responses as acquired maternal behaviors. Projection-specific chemogenetic silencing demonstrated that only SMT modulates OFC activity during pup retrieval. These findings demonstrate SMT as a previously uncharacterized thalamic hub shaping cortical representations of maternal behavior. HighlightsO_LIOFCRbp4 neurons receive strong inputs from higher-order thalamic nuclei (SMT, MD). C_LIO_LISMT and MD show complementary axonal projections across prefrontal cortical cortex. C_LIO_LISMT ensembles encode pup retrieval with experience-dependent plasticity. C_LIO_LISMT inputs selectively modulate pup retrieval representation in OFCRbp4 neurons. C_LI

neuroscience↗

bioRxiv2025

Arabidopsis aneuploidy mutant C30-81-as6, possesses enormous variations in multiple phenotypic characteristics.

Heavy-ion beam irradiation can be recognized as one of the powerful mutagenesis techniques because it induces high mutation frequency, minimal damage to the other traits and the possibility of having large DNA fragmental mutations. Aneuploid cells may have an additional or fewer number of chromosomes compared to their wild-type. The mutant line of C30-81-as6 is an ion beam-generated, Arabidopsis Col-0 based, aneuploid mutant line confirmed by whole genome sequence analysis, DNA quantity measurement using flow cytometry analysis and microscopic observations of additional chromosome. The mutant shows abnormal leaf shapes, petioleless rosette leaves, elevated trichome bases and later flowering phenotypes. Segregation analysis confirmed that additional DNA amount is correlated with observed phenotype since mutants showing intermediate phenotype possess moderate DNA quantities. A set of candidate causal genes was identified using up and downregulated differentially expressed genes in transcriptome analysis. Gene ontology analysis further supports mutant phenotypic characteristics and provides insights into its functional priorities, including promotion of cellular structure and energy production. Meanwhile, the downregulation of senescence-related gene ontology terms validates its extended vegetative phase. The whole genome sequence analysis based chromosome rearrangement prediction and the gene density mapping of upregulated DEGs, suggested that the long arm of chromosome 2 is a main component of the additional chromosome. In addition, the phenotype of C30-81-as6 largely resembles Arabidopsis additional chromosome 2 containing aneuploidy mutant. The ion beam mutagenesis generated aneuploidy mutant that may possess a fused DNA fragmented chromosome and it may successfully challenge the wild-type plants for establishment in nature.

genetics↗

bioRxiv2025

Dissecting Medullary Raphe Neurons Regulating Multiple Thermogenic Pathways

Thermogenesis is critical for survival and health in mammals. Although the thermoregulatory systems in the preoptic area are well documented, the downstream processing of these central signals--particularly by medullary neurons involved in the control of shivering and sympathetic activation of brown adipose tissue (BAT)--remains incompletely understood. Here we show that vesicular glutamate transporter type 3 (vGluT3)-expressing neurons in the medullary raphe pallidus (RPa) become active immediately before a spontaneous increase in body temperature. These neurons remain inactive under experimentally induced hypometabolic conditions and are necessary for rapid recovery from hypothermia. Furthermore, they communicate with multiple brainstem systems involved in the integration of thermal cues. Notably, RPa-vGluT3 neurons can drive shivering via specific brainstem premotor neurons, in addition to regulating sympathetic outflows for BAT thermogenesis and heat-conserving piloerection. These data indicate that RPa-vGluT3 neurons function as medullary hubs, coordinating sympathetic and somatic motor outputs to increase body temperature. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/673572v1_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@12d2e79org.highwire.dtl.DTLVardef@1463498org.highwire.dtl.DTLVardef@27058eorg.highwire.dtl.DTLVardef@1ddee56_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIRaphe pallidus-vGluT3 neurons are active immediately preceding a spontaneous rise in body temperature. C_LIO_LIThey are suppressed during the state of Q-neuron-induced hypothermia and hypometabolism (QIH). C_LIO_LIThey connect with multiple brainstem pathways involved in thermoregulation. C_LIO_LIThey control shivering via brainstem somatic premotor neurons. C_LI

neuroscience↗

bioRxiv2025

Bioengineered iPSC Vessels Recapitulate Human Vascular Physiological Function and Aging Phenotypes

Vascular aging contributes to multisystem diseases and limits health span. Although various animal models have contributed to aging research, their vasculatures poorly recapitulate human physiology. Even existing tissue-engineered blood vessels fail to mimic human vascular function and pathology, hindering translational advances in vascular aging studies. Here, we present a novel human physiological vascular model fabricated via the unique molding-induced circumferential alignment of human induced pluripotent stem cell (iPSC)-derived vascular smooth muscle cells with luminally seeded endothelial cells. This architecture enabled dynamic vasodiameter changes in response to vasoactive stimuli, including hormones and intraluminal pressure. Using iPSCs from a patient with Werner syndrome, the model recapitulated aging-associated phenotypes, such as hypercontractility and increased vascular compliance, possibly due to impaired nitric oxide bioavailability. Transcriptomic and metabolomic analyses revealed age-related dysregulation consistent with vascular senescence. As a key advantage of the vasculature, spatial transcriptomic analysis demonstrated upregulation of the aging marker CDKN1A near the lumen and downregulation of COL6A1 and TPM1 throughout the vessel. Treatment with mitochonic acid 5, a mitochondria-targeted compound, significantly reversed the aging phenotypes. These findings demonstrate that our engineered vascular model recapitulates key aspects of human vascular properties and provides a platform for mechanistic studies of vascular aging and drug discovery aimed at extending health span.

bioengineering↗

bioRxiv2025

Ex vivo live imaging unveils the dynamics of oocyte formation in mice

Oocyte formation in mammals is a tightly regulated process essential for female fertility, yet the underlying mechanisms remain poorly understood. In this study, we establish an ex vivo culture system that faithfully recapitulates in vivo development and enables long-term live imaging of mouse fetal ovaries. Using high resolution imaging, we capture the dynamic behaviors of germ cells during the development from oogonia to nascent oocytes. We identify pronounced blebbing activity during the mitosis-to-meiosis transition. This behavior is regulated by meiotic initiation signals, underscoring its potential developmental relevance, although its precise role remains unclear. A prevailing model suggests that oocyte formation involves organelle transfer from neighboring germ cells during cyst breakdown. However, through photoconversion-based tracking, we observe no detectable transfer of mitochondria or centrosomes, as organelles remain confined to individual cells. These findings point to alternative mechanisms for cytoplasmic enrichment in oocytes. Our study provides new insights into mammalian oocyte formation and establishes a powerful platform for analyzing germ cell dynamics in real time.

developmental biology↗