Biology subjects

Goto, R.

Publications and source records attributed to Goto, R..

5 recordsLinked to original sources

bioRxiv2026

Transcriptomic response to histone deacetylase inhibitors in cultured feline cells

ObjectiveIn recent years, the number of cats kept as companion animals has increased, leading to a growing demand for veterinary care. Although some histone deacetylase (HDAC) inhibitors are promising for the treatment of human cancers and neurological diseases, comprehensive systematic research on HDAC inhibitors in domestic cats remains insufficient. Therefore, this study aimed to investigate the effects of HDAC inhibitors on the transcriptome of feline cells. MethodsTwo types of cells derived from domestic cats, Crandell-Rees Feline Kidney (CRFK; kidney-derived) cells and PG-4 cells (astrocyte-derived), were treated with four HDAC inhibitors (panobinostat, trichostatin A, valproic acid, and vorinostat) for 24 h. Transcriptomic changes after treatment were examined using RNA sequencing. ResultsHDAC inhibitor treatment upregulated the expression of intercellular chemical interactions and signal transduction-related genes, similar to observations in human cells. Although HDAC inhibitors did not suppress the expression of cell cycle-related genes in CRFK cells, as observed in human cells, the inhibitors downregulated the expression of organogenesis-related genes. Consistent with observations in human cells, HDAC inhibitors suppressed the expression of cell cycle- and cancer-related genes in PG-4 cells. Importantly, valproic acid, which is thought to be more effective for neurological diseases than for cancer, suppressed the expression of more cancer-related genes in PG-4 cells than the other three HDAC inhibitors. Conclusion and relevanceOur findings revealed that the responses of cells derived from feline organs to various HDAC inhibitors varied considerably depending on the organ of origin and species. Since few studies, including human studies, have comprehensively compared transcriptomic responses to multiple HDAC inhibitor classes across multiple cell types, the results of this study provide a foundation for future research on the treatment and prevention of cancer and neurological diseases in domestic cats and other mammals.

cell biology↗

bioRxiv2025

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits

Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, we perturbed all expressed genes across 22 million primary human CD4+ T cells from four donors and developed a probe-based perturb-seq platform to measure the transcriptome effects in cells at rest and after stimulation. These data allow us to map genes that regulate known and novel pathways, including novel regulators of cytokine production. Importantly, active regulators and the gene programs they control change dramatically across stimulation conditions. Perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of Th1 and Th2 polarization and of age-related T cell phenotypes. Finally, we leveraged perturb-seq to implicate context-specific gene regulatory pathways in autoimmune disease risk. Our data provide a foundational resource to decode human immune function and genetic variation and for new approaches to study gene regulatory networks.

genetics↗

bioRxiv2025

Whole-genome sequencing of CRFK and PG-4 cells to infer the phenotype of the original donors

BackgroundCrandell-Rees Feline Kidney (CRFK; kidney-derived) cells and PG-4 cells (astrocyte-derived) have been in use and have been passaged for decades in laboratories worldwide; however, no detailed information on the genetic background of the donor individuals is available, particularly regarding phenotype characteristics such as coat and iris color. ResultsWe performed whole-genome sequencing of CRFK and PG-4 cells. We analyzed the resulting data to infer the phenotype of the individual from which the cells were derived, specifically for the coat color, coat length, coat pattern, and iris color. Our data suggested that CRFK cells originated from a cat with long black fur lacking stripes and with non-blue irises; PG-4 cells originated from a cat with long bicolored white and black fur without stripes, and with non-blue irises. Analysis of publicly available RNA-seq data confirmed that genes associated with coat phenotype and iris color are expressed in the skin and eyes, as well as in various other organs. ConclusionsVariants of the genes affecting coat phenotype and iris color may influence physiological functions throughout the body. These results shed light on the previously unknown genetic background of commonly used feline cultured cells and the phenotype of the donor individuals. These findings may facilitate more accurate interpretation of data obtained from cultured feline cells and provide guidelines for developing cell lines with domestic cat genotypes exhibiting diverse phenotypes through genome editing. This will help to provide clarity regarding deafness in cats with white fur and blue irises and elucidate the effects of melanocyte destruction caused by KIT gene mutations on the nervous system and the influence of other coat-related factors in organs other than the skin or functions independent of coat formation.

genomics↗

bioRxiv2025

Common tissue-specific expressions and regulatory mechanisms of c-KIT isoforms with and without GNNK and GNSK sequences across five mammals

c-KIT is a transmembrane receptor tyrosine kinase involved in various signaling pathways. Alternative pre-mRNA splicing of KIT results in isoforms that differ in the presence or absence of four amino acid sequences in the extracellular juxtamembrane region, such as, isoforms with and without the GNNK sequence (GNNK+ and GNNK-, respectively) in humans and mice, and those with and without GNSK (GNSK+ and GNSK-, respectively) in domestic dogs, cats, and sheep. These isoforms have been extensively studied as disease-associated (particularly tumors or cancer) splice variants with differing kinase activities. However, the expression patterns and regulatory factors of each isoform in various animal species without tumors or cancer remain poorly understood. Studying these aspects can provide the basis for understanding the associations between c-KIT isoforms and disease. Therefore, in the present study, a comprehensive expression analysis of c-KIT isoforms was conducted using tissue-wide transcriptome data from humans, mice, dogs, cats, and sheep. We found that the expression ratio of c-KIT isoforms differs across tissues, and such features are conserved across animal species: GNNK+ and GNSK+ isoforms have high expression ratios in the central nervous system, while GNNK- and GNSK- predominate in other tissues. Furthermore, NOVA2, RBFOX1, RBFOX3, and DYRK1A were suggested to be candidate factors regulating the selection of the alternative 5' splice donor site of KIT.

bioinformatics↗

bioRxiv2025

Remote Cortical Network for Frontal Cognitive Symptoms derived from Tau Accumulation in Progressive Supranuclear Palsy

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterized by impaired movement and frontal cognitive dysfunctions. While motor symptoms have been linked with subcortical tau deposits, network mechanisms underlying the frontal cognitive symptoms remain unclear because pathological tau accumulation is quite limited within the frontal cortex and heterogeneously distributed primarily in the subcortical regions. Here, we combined tau-PET using a high-contrast probe we have recently developed with normative connectome to resolve this issue. Tau-deposition sites were connected to a common cortical network that could not be identified through similar analyses based on atrophy detected by structural MRI. This network was predominantly overlapped with canonical action-mode and frontoparietal networks, which jointly support adaptive and goal-directed behavior. Critically, while the degree of subcortical primary tau deposition correlated with motor symptoms, only the degree of connectivity from tau-deposition sites to the derived cortical network explained the frontal cognitive deficits of individual patients. These findings suggest a novel mechanism that frontal cognitive impairments, but not motor deficits, in PSP are derived from remote effects of tau deposits, independent of atrophy, through the convergent connectivity to the identified common cortical network.

neuroscience↗