Biology subjects

Kashima, M.

Publications and source records attributed to Kashima, M..

14 recordsLinked to original sources

bioRxiv2026

Interleukin-11 promotes the colonic epithelial organoid regeneration from mechanical disruption

The intestinal epithelium relies on rapid repair to maintain homeostasis after injury, and dysregulation of this process contributes to the pathogenesis of inflammatory bowel disease and colorectal cancer. Interleukin-11 (IL-11), a fibroblast-derived cytokine elevated in these diseases, has well-documented effects on stromal cells, but its direct action on intestinal epithelial cells remains poorly characterized. Here, we used mouse colon organoids as an isolated epithelial system to directly examine the effects of IL-11 on epithelial cells. IL-11 stimulation activated the canonical JAK/STAT3 pathway, as evidenced by increased STAT3 phosphorylation and Socs3 induction in a concentration-dependent manner. In a pipetting-based mechanical disruption model, IL-11 significantly increased the number of organoids recovered. Although mechanical disruption dominated the overall transcriptional landscape, RNA-seq analysis identified coordinated upregulation of STAT3 target genes and proliferation-related pathways specifically in response to IL-11. Pharmacological inhibition of STAT3 attenuated the IL-11-induced promotion of organoid recovery, indicating that STAT3 signaling mediates the epithelial response to IL-11 and maintains organoid size under basal conditions. Together, these findings demonstrate that IL-11 directly promotes intestinal epithelial repair after mechanical disruption through STAT3-dependent signaling, providing a mechanistic basis for its protective role in acute colonic injury.

cell biology↗

bioRxiv2026

hB-PAC: A non-invasive aging clock for quantifying individual differences in aging

Quantifying differences in aging among individuals of the same chronological age could provide a direct measure of biological aging. However, existing methods often estimate biological age by predicting chronological age and treat such individual differences as prediction errors. We developed InferAging, a framework that estimates biological age by explicitly modeling individual deviations from chronological age. In progeroid zebrafish (klotho mutant; kl-/-), InferAging identified accelerated and delayed agers within the same chronological age group. A non-invasive variant using behavioral and morphological snapshots reproduced the transcriptome-integrated estimates without molecular input or lifelong tracking. The inferred aging state was associated with metabolic decline, intestinal barrier dysfunction, inflammation, and mucosal immune abnormalities beyond chronological age. These results demonstrate that non-invasive phenotypes can reveal molecularly supported individual aging states.

systems biology↗

bioRxiv2026

Multi-omics definition of the sex-specific glycoproteome of murine tissues

Sex-specific differences in the glycoproteome remain poorly defined despite growing evidence that protein glycosylation is a key determinant of sex biology. Here we present a tissue-resolved glycoproteome atlas of adult male and female C57BL/6J mice, integrating transcriptomics, proteomics and glycoproteomics with sialic acid speciation and lectin microarray profiling across 19 tissues. Quantitative analysis of >26,800 protein- and site-specific N-glycoforms from 1,512 glycoproteins revealed highly distinct tissue glycoproteomes shaped by coordinated regulation of protein abundance and glyco-enzyme expression. Multi-omics integration identified strong glycophenotype-enzyme relationships, including control of tissue sialylation by Cmas and Cmah, suggesting rate-limiting roles in glycosylation. Pronounced sex-linked glycophenotypes were observed in salivary gland, liver and kidney, driven by differences in fucosylation, sialylation and protein abundance, whereas the brain glycome was largely conserved between sexes. An interactive online database (https://igcore.cloud/mta/atlas-viewer/) provides a resource for exploring sex-biased glycosylation across mouse tissues.

cell biology↗

bioRxiv2025

Maternal care during early development is necessary for the acquisition of a calming response to back stroking

In many mammals, early postnatal interactions between caregivers and offspring involve rich physical contact, including stroking, holding, and grooming. Offspring typically remain calm and close to the caregiver during such stimulation. Although these behaviors are thought to support emotional regulation and bonding during infancy, the underlying mechanisms and the role of prior experience remain unclear. Here, we demonstrate that back stroking induces a conserved calming response in both human infants and mouse pups, characterized by reduced movement and heart rate. In mouse pups, stroking further facilitated sleep onset, increased EEG delta power, and attenuated stress-induced corticosterone elevations. These sleep-promoting and stress-buffering effects were absent in artificially reared pups deprived of postnatal maternal contact, underscoring the importance of early tactile experience. Transcriptomic analysis revealed downregulation of the voltage-gated calcium channel subunit gene Cacna1b in the hypothalamus of artificially reared pups. Moreover, knockdown of hypothalamic Cacna1b in maternally reared pups abolished stroking-induced calming and sleep-promoting effects. This study identifies a conserved, experience-dependent calming response to affiliative tactile input, biologically embedded through plasticity, that supports physiological regulation and stress resilience during early development. Our results highlight that affiliative tactile sensation, like discriminative tactile sensation, depends on early experience to organize neural mechanisms regulating internal states. SignificanceEarly-life physical contact with caregivers is essential for healthy emotional and physiological development in mammals, but its underlying mechanisms remain unclear. We show that back stroking induces a conserved calming response in both human infants and mouse pups, reducing movement, heart rate, and promoting sleep. These effects depend on early tactile experience and are mediated by Cacna1b expression in the hypothalamus. Our findings identify a plastic, experience-dependent pathway through which affiliative tactile input modulates internal states, revealing how parental care supports stress resilience and sleep physiology during early development.

neuroscience↗

bioRxiv2025

Systematic measurements of dose-dependent responses for combinatorial treatments of SA and JA led to the development of transcriptomic biomarkers

Plants coordinate defence against pathogens and herbivores through the crosstalk between salicylic acid (SA) and jasmonic acid (JA) signalling pathways. However, little is known about how plants integrate the phytohormone concentration profiles to shape defence states in complex field environments. Here we show that systematically varying combinatorial SA and JA concentrations in Arabidopsis thaliana reveals 43 distinct combination-specific transcriptional signatures beyond SA-JA antagonism. Leveraging these data, we developed and validated machine-learning-based transcriptomic biomarkers that enabled independent quantification of SA and JA response states. By applying these biomarkers to field-grown A. thaliana, we revealed that SA/JA response states were dynamically shaped by abundant and co-occurrence of herbivores on individual plants. Our study provides a strategy to decode hormonal responses to biotic environments from field transcriptomes, bridging the gap between molecular signalling and ecological dynamics.

plant biology↗

bioRxiv2025

Photoperiod decoder 1 regulates seasonal changes in energy metabolism through the growth hormone signaling pathway

Seasonal changes in metabolism are crucial for animals to adapt to annual environmental fluctuations. However, the molecular mechanisms underlying these adaptations remain poorly understood. Here, we identified a novel gene, photoperiod decoder 1 (phod1), which exhibits a unique bimodal expression pattern under long-day conditions in Japanese medaka fish (Oryzias latipes). While phod1 is conserved across many vertebrates, except for eutherians, its function remained unknown. Single-cell RNA sequencing analysis revealed that phod1 is predominantly expressed in specific pituitary cells that co-express opsin and circadian clock genes. Transcriptomic analysis using phod1 knockout fish demonstrated that phod1 is essential for photoperiodic regulation of growth hormone. Furthermore, transcriptomic and metabolomic analyses of the liver, the primary target of growth hormone, revealed significant alterations in energy metabolism. Behavioral analysis also showed that phod1 knockout fish exhibited significantly reduced locomotor activity. These findings indicate that phod1 plays a crucial role in seasonal metabolic adaptation through modulation of the growth hormone signaling pathway.

physiology↗

bioRxiv2021

Fillable and Unfillable Gaps in Rice Transcriptome under Field and Controlled Environments

The differences between plants grown in field and controlled environments have long been recognised; however, few studies have addressed the underlying molecular mechanisms. Here, we show fillable and unfillable gaps in the transcriptomes of rice grown in field and controlled environments by utilising SmartGC, a high-performance growth chamber that reproduces the fluctuating irradiance, temperature, and humidity of field environments. Rice transcriptome dynamics in SmartGC mimicked those in the field, particularly during the morning and evening; those in conventional growth chamber conditions did not. Further analysis revealed that fluctuation of irradiance affects transcriptome dynamics in the morning and evening, while fluctuation of temperature only affects transcriptome dynamics in the morning. We found upregulation of genes related to biotic and abiotic stress, whose expression was affected by environmental factors that cannot be mimicked by SmartGC. Our results accelerate the understanding of plant responses to field environments for both field and laboratory studies.

plant biology↗

bioRxiv2021

Artificial mimicry of seasonal transcriptome dynamics in Arabidopsis thaliana reveals short- and long-term responses to environmental conditions

Plants must respond to various seasonally changing environmental stimuli. In a previous study, seasonally oscillating genes were identified by a massive time-series transcriptome analysis for the wild population of Arabidopsis halleri ssp. gemmifera, a sister species to Arabidopsis thaliana. It was not clear how environmental stimuli shaped the seasonal expression pattern of these seasonally oscillating genes. In this study we show that responses in different time-scales contributed to the formation of seasonal expression patterns for several genes. To analyze the seasonally oscillating genes, we established an experimental system to mimic seasonal expression trends using A. thaliana and a "smart growth chamber mini," a hand-made low-cost small chamber. Arabidopsis thaliana plants were cultured under conditions that mimicked the average monthly temperatures and daylengths under different day-scale incubation. In total, the seasonal trends of 1627 seasonally oscillating genes were mimicked, and they showed varying temporal responses (constant, transient, and incremental) to environmental stimuli. Our results suggest that plants perceive and integrate information regarding environmental stimuli in the field by combining seasonally oscillating genes with different temporal responsiveness.

plant biology↗

bioRxiv2021

RNA-Seq data analysis for Planarian with tensor decomposition-based unsupervised feature extraction

RNA-Seq data analysis of non-model organisms is often difficult because of the lack of a well-annotated genome. However, in non-model organisms, contigs can be generated by de novo assembling. This can result in a large number of transcripts, making it difficult to easily remove redundancy. A large number of transcripts can also lead to difficulty in the recognition of differentially expressed transcripts (DETs) between more than two experimental conditions, because P-values must be corrected by considering multiple comparison corrections whose effect is enhanced as the number of transcripts increases. Heavily corrected P-values often fail to take sufficiently small P-values as significant. In this study, we applied a recently proposed tensor decomposition (TD)-based unsupervised feature extraction (FE) to the RNA-seq data obtained for a non-model organism, planarian Dugesia japonica; Although we used de novo assembled transcriptome reference with high redundancy, we successfully obtained a larger number of transcripts whose expression was altered between normal and defective samples as well as during time development than those identified by a conventional method. TD-based unsupervised FE is expected to be an effective tool that can identify a substantial number of DETs, even when a poorly annotated genome is available.

bioinformatics↗

bioRxiv2021

Intracellular and intercellular gene regulatory networks inference from time-course individual RNA-Seq

Gene regulatory network (GRN) inference is an effective approach to understand the molecular mechanisms underlying biological events. Generally, GRN inference mainly targets intracellular regulatory relationships such as transcription factors and their associated targets. In multicellular organisms, there are both intracellular and intercellular regulatory mechanisms. Thus, we hypothesize that GRNs inferred from time-course individual (whole embryo) RNA-Seq during development can reveal intercellular regulatory relationships (signaling pathways) underlying the development. Here, we conducted time-course bulk RNA-Seq of individual mouse embryos during early development, followed by pseudo-time analysis and GRN inference. The results demonstrated that GRN inference from RNA-Seq with pseudo-time can be applied for individual bulk RNA-Seq similar to scRNA-Seq. Validation using an experimental-source-based database showed that our approach could significantly infer GRN for all transcription factors in the database. Furthermore, the inferred ligand-related and receptor-related downstream genes were significantly overlapped. Thus, the inferred GRN based on whole organism could include intercellular regulatory relationships, which cannot be inferred from scRNA-Seq based only on gene expression data. Overall, inferring GRN from time-course bulk RNA-Seq is an effective approach for understanding the regulatory relationships underlying biological events in multicellular organisms.

bioinformatics↗

bioRxiv2020

DeLTa-Seq: direct-lysate targeted RNA-Seq from crude tissue lysate.

Using current mRNA quantification methods such as RT-qPCR and RNA-Seq, it is very difficult to examine thousands of tissue samples due to cost and labor of RNA extraction and quantification steps. Here, we developed Direct-RT buffer in which homogenization of tissue samples and direct-lysate reverse transcription can be conducted without RNA purification. We showed that appreciate concentration of DTT prevented RNA degradation but not RT in the lysates of several plants tissues, yeast, and zebrafish larvae. Using the buffer, direct reverse transcription on the lysates could produce comparable amount of cDNA with that synthesized from purified RNA. Furthermore, we established DeLTa-Seq (Direct-Lysate reverse transcription and Targeted RNA-Seq) method. DeLTa-Seq is a cost-effective, high-throughput and highly-precise quantification method for the expressions of hundreds of genes. It enables us to conduct large-scale studies using thousands of samples such as chemical screening, field experiments and studies focusing on individual variability.

molecular biology↗

bioRxiv2019

Transcriptional variation in glucosinolate biosynthetic genes and inducible responses to aphid herbivory on field-grown Arabidopsis thaliana

Recently, increasing attempts have been made to understand how plant genes function in natura studies. To determine whether plant defense genes are activated under multiple biotic stimuli, we combined a high-throughput RNA-Seq with insect survey data on 19 accessions of Arabidopsis thaliana growing on the field site of Switzerland. We found that genes with GO annotations "glucosinolate biosynthetic process" and "response to insects" were the most significantly enriched, exhibiting largely variable expression among plant accessions. Nearly half of the total expression variation in glucosinolate biosynthetic genes, AOPs, ESM1, ESP, and TGG1, was explained by among-accession variance. Combined with the field RNA-Seq data, bioassays confirmed that AOP3 was up-regulated in response to the mustard aphid Lipaphis erysimi. In addition, we also found that the expression of a major cis-jasmone activated gene CYP81D11 was positively correlated with the number of the flea beetles Phyllotreta spp. The combined results from RNA-Seq and insect surveys suggested that plants can activate their defenses even when they are exposed to multiple biotic stimuli in natura.

plant biology↗

bioRxiv2018

High-throughput RNA-Seq analysis on plant response under fluctuating temperature conditions

RNA-Seq is a whole-transcriptome analysis method used to research biological mechanisms and functions; its use in large-scale experiments is limited by costs and labour. In this study, we established a high-throughput and cost effective RNA-Seq library preparation method that did not require mRNA enrichment. The method adds unique index sequences to samples during reverse transcription (RT) that is conducted at a higher temperature ([≥]62{degrees}C) to suppress RT of A-rich sequences in rRNA, and then pools all samples into a single tube. Both single-read and paired end sequencing of libraries is enabled. We found that the pooled RT products contained large amounts of RNA, mainly rRNA, and caused over-estimations of the quantity of DNA, resulting in unstable tagmentation results. Degradation of RNA before tagmentation was necessary for the stable preparation of libraries. We named this protocol low-cost and easy RNA-Seq (Lasy-Seq), and used it to investigate temperature responses in Arabidopsis thaliana. We analysed how sub-ambient temperatures (10-30{degrees}C) affected the plant transcriptomes, using time-courses of RNA-Seq from plants grown in randomly fluctuating temperature conditions. Our results suggest that there are diverse mechanisms behind plant temperature responses at different time scales.

plant biology↗

bioRxiv2018

Prediction of environmental response in field-grown rice using expression-dynamics-QTL

How genetic variations affect gene expression dynamics of field-grown plants remains unclear. Using statistical analysis of large-scale time-series RNA-sequencing of field-grown rice from chromosome segment substitution lines (CSSLs), we identified 1675 expression dynamics quantitative trait loci (edQTLs) leading to polymorphisms in expression dynamics under field conditions. Based on the edQTL and environmental information, we successfully predicted gene expression under environments different from training environments, and in rice cultivars with more complex genotypes than the CSSLs. Overall, edQTL identification helped understanding the genetic architecture of expression dynamics under field conditions, which is difficult to assess with laboratory experiments1.The prediction of expression based on edQTL and environmental information will contribute to crop breeding by increasing the accuracy of trait prediction under diverse conditions.

bioinformatics↗