Biology subjects

Nakamura, Y.

Publications and source records attributed to Nakamura, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

An iPSC-based experimental framework for investigating phenotypic variation associated with Jomon ancestry in the present-day Japanese population

Ancestry-related genomic variation may contribute to phenotypic diversity. However, its cellular consequences remain difficult to evaluate. To address this, we developed a human induced pluripotent stem cell (hiPSC)-based framework for investigating such phenotypes. We used the Japanese population as a model of Jomon-related and continental East Asian ancestry admixture. Jomon ancestry, estimated using the Jomon allele score (JAS), was associated with clinical measures, including renal-related traits and serum triglycerides in 34,152 Tohoku Medical Megabank participants. Peripheral blood mononuclear cell transcriptomics of donors from the upper and lower extremes of the JAS distribution (n = 10) suggested group-level differences in immune-related gene expression. To test whether the serum triglyceride association coincided with hepatic cellular phenotypes, we differentiated hiPSCs from these donors into hepatocyte-like cells. Neither intracellular triglycerides nor lipid-related gene expression differed between groups. These findings highlight the value of a genetically characterized hiPSC-based framework for investigating ancestry-associated phenotypes across cellular contexts.

genomics↗

bioRxiv2026

PLCXD2 preferentially hydrolyzes phosphatidylinositol and supports retinal lipid homeostasis and photoreceptor integrity

PLCXD proteins have been linked to phosphoinositide metabolism for more than a decade, and PLCXD2 activity has been associated with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] depletion, yet its preferred direct substrate has remained unresolved. Here, cellular lipidomics showed that catalytically active PLCXD2 reduced the major phosphatidylinositol (PI) 38:4 species, with more modest phosphoinositide changes and increased diacylglycerol (DAG) and phosphatidic acid (PA). Using recombinant PLCXD2 and acyl-chain-matched substrates, we found that PLCXD2 hydrolyzed PI substantially more efficiently than PI(4,5)P2 and most other phosphoinositides tested. In Plcxd2-deficient retina, PI abundance was preserved, whereas DAG and PA were reduced without broad changes in major membrane phospholipid classes. PLCXD2 loss was associated with early structural abnormalities at the photoreceptor-bipolar synaptic interface, followed by outer nuclear layer thinning and reduced electroretinographic a-wave responses. These findings identify PLCXD2 as a PI-preferring mammalian PLC and reveal an endogenous role in retinal lipid homeostasis and outer retinal integrity.

biochemistry↗

bioRxiv2026

From neuropeptide and receptor annotation to ligand-receptor pairing: a sequence- and structure-based framework for mapping the neuropeptide-receptor interactome in Gryllus bimaculatus

Neuropeptides and their G protein-coupled receptors (GPCRs) control much of insect physiology and behaviour, but in Gryllus bimaculatus, an emerging model and edible insect, receptor sequence similarity hinders the mapping of which peptide each GPCR activates. We re-annotated a chromosome-scale genome (BUSCO 95.3%, from 86.7% on insecta_odb12) with comprehensive curation of 48 neuropeptide precursor families (51 loci, including seven not previously identified) and 134 candidate GPCRs (66 rhodopsin-class, 68 secretin-class), providing a near complete neuropeptide-receptor interactome catalogue. We modelled all 15,946 peptide-receptor pairs with AlphaFold3 and Boltz-2 and scored each interface with pLDDT and ipSAE. Ranking these scores, and cross-checking the top candidate for each family against a receptor phylogeny of known ligand specificity, gave a confident, phylogenetically related receptor for 27 of 35 curated receptor groups. These matches confirm the structural scorings with existing deorphanization data and propose receptors for peptides with no prior functional evidence. The annotation, curated peptide and receptor sets, and ranked complexes are available through CricketBase (https://cricket.annotation.jp), a genome browser with a structure viewer of peptide-receptor complexes, providing a resource for G. bimaculatus endocrinology and a workflow to deorphanize GPCRs in other non-model insects.

bioinformatics↗

bioRxiv2026

Hypothalamic neurosecretory protein GM causes fat deposition and suppresses gonadal maturation in Japanese quail

Introduction: Central regulation of energy homeostasis is essential for balancing lipid storage and reproductive investment; however, the hypothalamic factors governing this trade-off remain incompletely defined in birds. Neurosecretory protein GM (NPGM), an 83-amino acid hypothalamic factor, was investigated for its role in energy allocation during sexual maturation in Japanese quail (Coturnix japonica). Methods: Male and female quails at the onset of sexual maturation received chronic intracerebroventricular administration of NPGM for 13 days via osmotic pumps, during which their body mass, food intake, and water intake were monitored daily. At the endpoint, peripheral tissue and muscle masses, serum metabolite levels (glucose, fatty acids, triglycerides, testosterone, and 17{beta}-estradiol), hepatic triglyceride content, and gene expression profiles of hypothalamic feeding/reproductive genes and hepatic/adipose lipid metabolic genes were evaluated. Results: NPGM increased subcutaneous and abdominal fat in both sexes and was associated with suppressed gonadal maturation, as indicated by reduced testicular mass relative to body mass and lower testosterone levels in males, as well as a trend toward reduced ovarian mass and lower 17{beta}-estradiol levels in females. Sex-dependent metabolic phenotypes emerged: males exhibited increased body mass gain, hyperphagia, elevated water intake, enlarged liver, pancreas, and heart, higher serum and hepatic triglyceride levels, increased hepatic SCD1 expression, and reduced hepatic CGI-58, PPAR{gamma}, SLC2A2, and CD36. In contrast, females showed fat accumulation without hyperphagia or hepatic triglyceride elevation, accompanied by reduced hepatic VTG2 and APOV1 and decreased adipose ATGL, LPL, and FATP. Hypothalamic AGRP expression decreased in males, whereas both NPY and AGRP decreased in females. Discussion: These findings demonstrate that central NPGM shifts energy allocation from reproduction toward lipid storage through sex-dependent endocrine and metabolic mechanisms, identifying NPGM as a neuroendocrine regulator of energy allocation during sexual maturation in Japanese quails.

neuroscience↗

bioRxiv2026

Whole genome sequences and annotations of Japanese and French strains of Heterosigma akashiwo

High-quality reference genomes provide an essential foundation for elucidating the molecular basis of organismal ecophysiology. Here, we sequenced and assembled chromosome-scale genomes of two Heterosigma akashiwo strains isolated from coastal waters of Japan and France. The assembly sizes were 1.18 Gb and 1.43 Gb for the Japanese and French strains, respectively. The scaffold N50 of the Japanese strain assembly was 66 Mb, whereas the one of the unscaffolded French strain assembly was 33 Mb. To our knowledge, these assemblies represent among the largest and most contiguous genome resources currently available for members of the Stramenopiles (Ochrophyta). Evidence-based gene prediction in the Japanese strain recovered approximately 90% of conserved stramenopile core genes, indicating a highly complete gene repertoire, and was complemented by extensive functional annotation. In the French strain, homology-based gene prediction recovered approximately 80% of conserved core genes. Comparative genome analysis revealed extensive synteny conservation between the two strains, although several putative duplication and translocation events were detected. These genomic resources provide a robust framework for investigating the molecular, cellular, and ecological mechanisms underlying the physiology, adaptation, and bloom-forming capacity of H. akashiwo.

genomics↗

bioRxiv2026

Global identification of neuronal and astrocytic integral membrane proteins that require Retromer for their endosomal recycling.

Efficient transport of membrane proteins through the endosomal network is essential for brain development and function, with perturbation implicated in disease. Deficiencies in Retromer, a key regulator of endosomal transport, have been linked to aging-related neurodegenerative disorders including Alzheimers and Parkinsons disease. To better define the neuroprotective role of Retromer, we have applied cell surface restricted proteomics to identify those integral membrane proteins whose recycling to the plasma membrane is mediated by Retromer and associated cargo adaptors, sorting nexin 3 (SNX3), its paralogue sorting nexin 12 (SNX12), and sorting nexin 27 (SNX27) (data available via ProteomeXchange: PXD078277). By comparing primary rat cortical neurons and astrocytes we have identified several cargoes that require either SNX3/SNX12- or SNX27-Retromer complexes for endosomal recycling, including proteins involved in synapse organisation, synaptic signalling and Alzheimers disease pathology. We highlight that perturbed Retromer function leads to endosomal enlargement, and we establish a key role of SNX27-Retromer in modulating transport of glutamate across both neuronal and astrocytic membranes via recycling of glutamate transporters EAAT3 (SLC1A1) and EAAT1 (SLC1A3) respectively. Our study provides further mechanistic insight into the consequences of Retromer deficiency for neuronal and astrocytic function, offering new avenues of research in the treatment of neurodegenerative disease. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=194 SRC="FIGDIR/small/724903v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@1225eedorg.highwire.dtl.DTLVardef@1863f1dorg.highwire.dtl.DTLVardef@99c21eorg.highwire.dtl.DTLVardef@976bfd_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Suppression of Retromer and the sorting nexins (SNX27, SNX3/SNX12) leads to a significant change in the surface proteome of rat cortical neurons and astrocytes. Focusing on the glutamate transporters, SLC1A1 and SLC1A3, we have validated that SNX27-Retromer is required for their trafficking, with SNX27-Retromer suppression in astrocytes leading to a loss of glutamate uptake. C_FIG

molecular biology↗

bioRxiv2026

Catalog of gut microbiota alterations associated with anticancer therapies across multiple cancer types

BackgroundAnticancer therapies can alter the gut microbiota and may affect gut bacteria associated with treatment response. However, most longitudinal studies have focused on specific cancer types or individual treatment regimens, and systematic analyses across diverse cancer therapies remain limited. We analyzed longitudinal fecal microbiota profiles using 16S ribosomal RNA gene amplicon sequencing in the pan-cancer SCRUM-Japan MONSTAR-SCREEN cohort. We included 528 paired pre- and post-treatment fecal samples from 264 patients with advanced solid tumors across 18 cancer types and characterized the gut microbiota alterations associated with 22 anticancer drugs and related clinical factors. ResultsAcross the cohort, Shannon diversity did not significantly change after treatment (mean, 3.81 vs. 3.78; P = 0.58), and pre- and post-treatment samples exhibited no clear separation in ordination space. However, within-patient analysis detected a subtle but significant longitudinal microbiota shift (paired PERMANOVA, P = 0.0001), highlighting the importance of accounting for paired sampling. Clustering of genus-level compositional alterations revealed patient groups with distinct degrees of microbiota alteration, with the largest shifts associated with antibiotic exposure, transition from normal stool to diarrhea, and specific treatment regimens. Multivariable regression analysis of 22 anticancer drugs identified drug-bacteria associations and demonstrated that drugs with similar mechanisms of action, including epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors, exhibited similar microbiota change profiles. Targeted analyses highlighted concordant reductions in the Christensenellaceae R-7 group among EGFR inhibitor-exposed patients and depletion of Faecalibacterium among immune checkpoint inhibitor-exposed patients. ConclusionsThis study provides a cross-cancer catalog of microbiota alterations associated with anticancer therapies and highlights therapy-related shifts in the gut ecosystem, including patterns shared by drugs with similar mechanisms of action.

microbiology↗

bioRxiv2026

Single-cell spatial multiomics identifies POSTN+ CAFs mediating chemoradiotherapy resistance in rectal cancer

Neoadjuvant chemoradiotherapy (CRT) is standard for locally advanced rectal cancer (LARC), yet many patients retain residual disease. To resolve CRT-associated remodeling of the tumor microenvironment, we generated a multimodal spatial atlas from serial sections of paired pretreatment and post-treatment specimens from 24 patients using Xenium single-cell spatial transcriptomics and PhenoCycler multiplex proteomics, profiling 2.8 million cells; matched Visium HD datasets were generated on adjacent serial sections. Resistance was most strongly associated with fibroblast and myeloid programs adjacent to residual tumor. We identify a periostin (POSTN)-expressing CAF subset selectively enriched around residual tumor cells in non-responders, displaying a myofibroblastic phenotype and activating extracellular matrix remodeling, noncanonical WNT signaling, and immunosuppressive pathways. Tumor cells neighboring POSTN+ CAFs show consistent epithelial-mesenchymal transition signatures. Together, this atlas enables interrogation of CRT-induced spatial remodeling and nominates POSTN+ CAFs as key mediators and targets of CRT resistance, with direct relevance to CRT-based combination strategies.

cancer biology↗

bioRxiv2026

An auxiliary protein tunes reductase activity in alkaloid biosynthesis

Monoterpene indole alkaloids encompass a diverse class of plant natural products. Many of these valuable compounds, including the anticancer medicines vinblastine and vincristine (Catharanthus roseus) and the antiaddiction treatment ibogaine (Tabernanthe iboga) utilize a common biosynthetic intermediate, 19E-geissoschizine, which is produced by the medium-chain dehydrogenase/reductase geissoschizine synthase (GS). Herein we report the discovery of a non-catalytic auxiliary protein (facilitator of geissoschizine synthase, FoGS) that improves formation of 19E-geissoschizine by acting in combination with GS. The discovery of a FoGS orthologue that works with GS to produce 19Z-geissoschizine shows how this protein also controls the stereochemistry of the product. We demonstrate that FoGS and GS interact to form a stable heterodimer, and show through mutagenesis that FoGS likely modulates the structure of the GS active site. Microscopy studies suggest that FoGS also changes the subcellular localization of GS. The discovery of FoGS will enable efforts to heterologously reconstitute commercially important geissoschizine-derived monoterpene indole alkaloids, and moreover, highlights how metabolic pathways utilize proteins that are not essential for production of the products, but nevertheless enhance the efficiency and specificity of the catalytic biosynthetic pathway components.

biochemistry↗

bioRxiv2025

Selective PPAR-α activation with pemafibrate attenuates macrophage-mediated progression of calcific aortic valve disease

BACKGROUNDCalcific aortic valve disease (CAVD) compromises valve compliance and cardiac hemodynamics leading to aortic stenosis (AS) and cardiovascular dysfunction. With treatment for severe AS limited to valve replacement and no effective pharmacotherapies, new interventions are urgently needed for patients. This study evaluated pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR) activator as a novel therapeutic for CAVD and AS. METHODS AND RESULTSIn an aortic valve wire injury (AVWI) model of AS in Ldlr-/- mice, pemafibrate administration (0.2 mg/kg/day) for 15 weeks improved aortic valve function and reduced valvular calcification by 39% (p<0.001), accompanied by reduced leaflet inflammation and CD68 macrophage infiltration. These effects were independent of changes in plasma triglyceride levels. In vitro, pemafibrate suppressed inflammation-mediated calcification of primary human valvular interstitial cells (VICs) by modulating macrophage-derived secreted factors, identifying macrophage-VIC crosstalk as a key disease mechanism. Direct treatment of macrophages with pemafibrate, or exposure to serum from pemafibrate-treated participants in the PROMINENT randomized controlled trial, shifted macrophages toward a less inflammatory and less chemotactic phenotype. Proteomic analyses of patient serum substantiated these findings by reflecting a systemic reduction in inflammatory parameters and monocyte activation. Network integration of the in vitro derived pemafibrate-responsive proteome with human calcified AV tissue proteomes identified aberrant protein translation (GNB2L1, GSPT1) and disrupted bioenergetics (MYDGF, PDIA4) as potential clinically relevant pemafibrate-responsive pathways and effector proteins relevant to AS progression. CONCLUSIONSPemafibrate slows experimental AS progression and valve calcification through modulation of macrophage-VIC crosstalk, independent of lipid lowering. These findings support further evaluation of pemafibrate as a potential pharmacological approach for CAVD and support further testing in randomized clinical trials.

pharmacology and toxicology↗

bioRxiv2025

Conserved early steps of stemmadenine biosynthesis

Stemmadenine acetate is a pivotal intermediate in the production of pharmacologically active monoterpene indole alkaloids. Here, we identify orthologs of stemmadenine acetate pathway genes (SGD, GS, GO, Redox1, Redox2, SAT) from Tabernanthe iboga. We characterize these enzymes in vitro, and additionally, we reconstitute stemmadenine acetate biosynthesis in Nicotiana benthamiana, comparing the formation of intermediates and shunt products that are produced when previously characterized orthologs from the related plant Catharanthus roseus are used. Ortholog pairs are catalytically indistinguishable, except in the case of GS. Surprisingly, the T. iboga ortholog catalyzes formation of an alternate stereoisomer 19Z-geissoschizine, seeding a low-flux Z-series in heterologous reconstitution systems in vitro and in planta. We additionally characterize the major shunt products that arose during reconstitution of stemmadenine acetate biosynthesis. We show that the substrate promiscuity of Redox2 results in formation of the shunt products 16(R/S)-isositsirikines, hampering pathway flux and yields. Additionally, we show that stemmadenine can be oxidized by endogenous N. benthamiana enzymes, leading to the shunt product condylocarpine. Nevertheless, we could produce stemmadenine at a 6 mg yield from 19E-geissoschizine by heterologous expression in N. benthamiana. Overall, we highlight the prospects for milligram production of important biosynthetic intermediates in N. benthamiana.

biochemistry↗

bioRxiv2025

Promotion of seed germination in Echinochloa crus-galli with atmospheric air plasma

Plasma technology has attracted increasing attention for potential agricultural applications, and it has been investigated for decades particularly for its ability to promote seed germination. However, most studies have focused on crop species, and little is known about its potential use for weed management. In this study, we examined whether air plasma influences the germination of Echinochloa crus-galli, a major paddy field weed. When seeds were cultivated without stratification, direct irradiation with air plasma did not enhance germination. In contrast, once dormancy was partially released by cold stratification, plasma treatment significantly promoted germination. Interestingly, the effect disappeared after prolonged chilling, when dormancy was completely released. These results suggest that plasma promotes germination by acting on the dormancy-breaking process. In addition, plasma-activated water (PAW) also stimulated germination, although its effect was weaker than that of gaseous plasma. Overall, this study demonstrates that air plasma can promote the germination of grass weed seeds, providing a potential strategy for weed control by inducing germination prior to crop seeding.

plant biology↗

bioRxiv2025

Human Interleukin-4-Dependent Facilitation of Human IgG Production in PBL-NOG-hIL-4-Tg mice

Immune-humanized mice provide valuable experimental models for evaluating immune-based therapies, yet the induction of human antigen-specific IgG production remains limited due to species-specific incompatibilities. Our previous work demonstrated that NOG-hIL-4-Tg mice, which express human interleukin-4 (IL-4), support human T and B cell maintenance and enable antigen-specific IgG production following transplantation of human peripheral blood mononuclear cells (PBMCs). In this study, we investigated how IL-4 enhances antibody responses in this model. Flow cytometry and histological analysis revealed that human B cell maintenance was associated with specific plasma hIL-4 concentration ranges at supraphysiological levels. T and B cell receptor repertoire analysis using next-generation sequencing showed that clonal diversity remained largely conserved for one month and decreased to three months post-engraftment. Immunoglobulin repertoire profiling confirmed IgG class switching in an IL-4-concentration-dependent manner. Among the IgG subclasses, IgG3 increased during the first and second months and then decreased thereafter. In contrast, IgG1 tended to increase over time; however, the proportion of IgG subclass varied among individual donors. Following immunization with two distinct peptide antigens, the mice produced enhanced levels of antigen-reactive IgG. However, many B cell clones also exhibited weak responses to unrelated third-party antigens, likely reflecting insufficient affinity maturation. Histological evaluation showed tertiary lymphoid structure (TLS)-like accumulations of B and T cells in the spleen, although fully developed germinal centers were absent. Taken together, these findings demonstrate that NOG-hIL-4-Tg mice maintain human B cells within a regulated IL-4 environment, promote early formation of splenic tertiary lymphoid structures, and support IgG production characterized by clonal expansion, class switching, and somatic hypermutation. These results confirm that human IL-4 expression supports human antibody responses in the PBL-NOG-hIL-4-Tg mouse system. (278)

immunology↗

bioRxiv2025

A phenotypic brain organoid atlas for neurodevelopmental disorders

Thousands of genes are associated with neurodevelopmental disorders (NDDs), yet mechanisms and targeted treatments remain elusive. To fill these gaps, we present a CIRM-initiated NDD biobank of 352 publicly-available genetically-diverse patient-derived iPSCs, along with clinical details, brain imaging and genomic data, representing four major categories of disease: microcephaly (MIC), polymicrogyria (PMG), epilepsy (EPI), and intellectual disability (ID). From 35 representative patients, we studied over 6000 brain organoids for histology and single cell transcriptomics. Compared with an organoid library from ten neurotypicals, patients showed distinct cellular defects linked to underlying clinical disease categories. MIC showed defects in cell survival and excessive TTR+ cells, PMG showed intermediate progenitor cell junction defects, EPI showed excessive astrogliosis, and ID showed excessive generation of TTR+ cells. Our organoid atlas demonstrates both conserved and divergent NDD category-specific phenotypes, bridging genotype and phenotype. This NDD iPSC biobank can support future disease modeling and therapeutic approaches. HIGHLIGHTSO_LIResource of 352 CIRM-funded genetically-diverse IPSC lines from patients with neurodevelopmental disorders (NDDs). C_LIO_LIGenome/exome and brain images available for these genetically-diverse IPSC lines. C_LIO_LIDerived human brain organoids (hBOs) show disease-specific histological and cellular phenotypes. C_LIO_LIhBO phenotypes show unanticipated differentiation towards non-neuronal cell fates in NDDs. C_LI

neuroscience↗

bioRxiv2025

GLP1 receptor agonists attenuate systemic inflammation through microbiota mediated enrichment of Faecalibacterium prausnitzii and Roseburia spp

This study investigated the comparative anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and nonsteroidal anti-inflammatory drugs (NSAIDs), with a particular focus on microbiota-mediated mechanisms. A total of 120 participants were enrolled, including a GLP-1 RA group (n = 60) and an NSAID control group (n = 60). After 12 weeks of treatment, the GLP-1 RA group showed significant reductions in systemic inflammatory markers, with C-reactive protein (CRP) decreasing from 4.3 {+/-} 0.6 to 2.1 {+/-} 0.4 mg/L (p < 0.01), interleukin-6 (IL-6) decreasing from 3.6 {+/-} 0.5 to 1.8 {+/-} 0.3 pg/mL (p < 0.01), and tumor necrosis factor- (TNF-) decreasing from 18.2 {+/-} 1.5 to 12.5 {+/-} 1.2 pg/mL (p < 0.05). In contrast, the NSAID group exhibited only modest reductions in these markers without achieving normalization. Microbiome analysis revealed a significant post-treatment enrichment of Faecalibacterium prausnitzii (r = -0.46 with CRP, p < 0.001) and Roseburia spp. (r = -0.39 with CRP, p < 0.01) in the GLP-1 RA group, whereas NSAIDs showed no comparable effect. These findings establish a novel mechanistic link between incretin-based therapies and host immune homeostasis, highlighting the potential of GLP-1 RAs as systemic anti-inflammatory agents beyond their metabolic benefits.

immunology↗

bioRxiv2025

Reliable Detection of SGLT2 Protein through Knockout-based Antibody Characterization and Optimized Procedures

IntroductionSodium-glucose cotransporter 2 (SGLT2) is a key mediator of renal glucose reabsorption. Its pharmacological inhibition exerts cardio- and reno-protective benefits. Despite widespread clinical interest, reliable detection of SGLT2 protein remains challenging due to concerns regarding the specificity of available antibodies. MethodsThis study assessed the specificity of eight commercially available anti-SGLT2 antibodies by immunohistochemistry and Western blotting. Genetically engineered Sglt2-deficient mice and rats, generated via clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology, were employed as definitive negative controls. Additionally, human kidney tissues, including renal cell carcinoma samples, were analyzed. ResultsAmong the antibodies tested, few exhibited robust specificity, characterized by substantial immunostaining with minimal background in wild-type kidney tissues and complete absence of staining in Sglt2-deficient samples. In renal cell carcinoma samples, a validated antibody detected SGLT2 immunostaining in proximal tubules of non-tumor regions but not in tumor areas. Subcellular localization studies revealed that SGLT2 was enriched within proximal tubular microvilli, partially overlapping with its co-factor PDZK1IP1 (MAP17). LRP2 (megalin) and NHE3 were placed at the microvillar base and did not colocalize with SGLT2. Western blotting identified a specific SGLT2 band at approximately 55 kDa in kidney lysates using several antibodies under optimized procedures. This band was shifted to approximately 45 kDa after enzymatic removal of N-linked glycans. One antibody detected a weak band at the same molecular mass even in kidney lysates from Sglt2-deficient rodents. ConclusionsConsiderable variability exists in the specificity of commercially available anti-SGLT2 antibodies. Only a limited number of antibodies are suitable for reliable detection of SGLT2 in rodent and human samples. Rigorous antibody characterization, including the use of knockout controls and optimized experimental conditions, is essential to ensure reproducibility and prevent misinterpretation in studies investigating the biological and pathophysiological roles of SGLT2.

molecular biology↗

bioRxiv2025

Chromosome-scale genomes of two wild flowering cherrys (Cerasus itosakura and C. jamasakura) provide insights into structural evolution in Prunus

Flowering cherries (genus Cerasus) are iconic trees in Japan, celebrated for their cultural and ecological significance. Despite their prominence, high-quality genomic resources for wild Cerasus species have been limited. Here, we report chromosome-level genome assemblies of two representative Japanese cherries: Cerasus itosakura, a progenitor of the widely cultivated C. xyedoensis Somei-yoshino, and Cerasus jamasakura, a traditional popular wild species endemic to Japan. Using deep PacBio long-read and Illumina short-read sequencing, combined with reference-guided scaffolding based on near-complete C. speciosa genome, we generated assemblies of 259.1 Mbp (C. itosakura) and 312.6 Mbp (C. jamasakura), with both >98% BUSCO completeness. Consistent with their natural histories, C. itosakura showed low heterozygosity, while C. jamasakura displayed high genomic diversity. Comparative genomic analyses revealed structural variations, including large chromosomal inversions. Notably, the availability of both the previously published C. speciosa genome and our new C. itosakura genome enabled the reconstruction of proxy haplotypes for both parental lineages of Somei-yoshino. Comparison with the phased genome of Somei-yoshino revealed genomic discrepancies, suggesting that the cultivar may have arisen from genetically distinct or admixed individuals, and may also reflect intraspecific diversity. Our results offer genomic foundations for evolutionary and breeding studies in Cerasus and Prunus.

genomics↗

bioRxiv2025

A lipid-driven, microbe-independent mechanism of acne via Lrig1+ follicular progenitor cells

Long-chain saturated fatty acids (lcSFAs) are abundant in the skin, but their pathogenic roles in acne remain unclear. In human sebum profiling, C16:0, the most abundant lcSFA, was the only fatty acid significantly elevated in acne and correlated with inflammatory comedone counts. We then established a mouse model that faithfully recapitulates human acne phenotypes, in which topical C16:0 penetrated the epidermis and induced sebocyte hyperplasia, comedogenesis, and follicular inflammation. Mechanistically, C16:0 activated keratinization and inflammatory pathways and drove sebocyte-lineage differentiation from Lrig1+progenitor cells, which function as cutaneous lipid sensors. These effects persisted in germ-free mice and were unaffected by fatty acid transporter modulation, while MyD88 signaling was partially required for inflammatory cell recruitment. Together, our findings identified C16:0 as a human acne-associated lipid that recapitulates disease hallmarks through a microbe-independent, lipid-driven pathway, highlighting Lrig1+cells as central hubs in remodeling of the pilosebaceous unit.

cell biology↗