Biology subjects

Shima, Y.

Publications and source records attributed to Shima, Y..

8 recordsLinked to original sources

bioRxiv2026

The Nkx2.3-Nr5a1 gene cascade plays a crucial role in spleen-specific vascular architecture and marginal zone formation

NR5A1 is a nuclear receptor and master regulator of steroidogenic tissue development and steroid hormone biosynthesis in the adrenal glands and gonads. Although NR5A1 is expressed in splenic vascular endothelial cells, its function in the adult spleen remains unclear. Using single-cell transcriptomics in mice, we show that NR5A1-positive endothelial cells are heterogeneous and exhibit distinct phenotypes according to their localization in the splenic sinus or marginal sinus. To assess NR5A1 function, we generated a spleen-specific Nr5a1 enhancer deletion model. Enhancer loss resulted in reduced spleen size and ablation of the marginal zone and marginal sinus. In addition, 21-hydroxylase activity in splenic sinusoidal endothelial cells was reduced, particularly in females, leading to decreased levels of adrenocortical steroids in the spleen. Enhancer deletion also induced ectopic lymphatic-like and high endothelial venule-like vasculature similar to those observed in Nkx2.3-deficient mice. Consistently, mutation of the NKX2.3-binding motif within the enhancer abolished NR5A1 expression. Together, these findings identify an Nkx2.3[->]Nr5a1 regulatory axis essential for spleen-specific endothelial cell differentiation and splenic architecture required for blood filtration and marginal zone formation.

developmental biology↗

bioRxiv2025

Foliar application of mixed DAMP- and MAMP-oligosaccharides enhances root growth and fruit yield in okra and tomato in greenhouse experiments

Plants perceive diverse endogenous and microbial molecular patterns that shape their defense, growth, and productivity. Damage-associated molecular patterns (DAMPs) such as cello- and xylo-oligosaccharides, and microbe-associated molecular patterns (MAMPs) such as chitin-oligosaccharides, are known to promote both development and immunity. Here, we evaluated the combined application of these three oligosaccharides (Oligo-Mix) in okra and cherry tomato under greenhouse conditions. Regular foliar treatment with Oligo-Mix enhanced root elongation and biomass accumulation, and increased fruit number and yield in both crops. RNA-seq analysis of Oligo-Mix-treated tomato leaves showed coordinated induction of photosynthetic genes, components of the translational machinery, cell-wall remodeling factors, and enzymes involved in flavonoid/anthocyanin biosynthesis, indicating broad enhancement of metabolic capacity and protective secondary pathways. Together, these results demonstrate that Oligo-Mix functions as a biostimulant that supports both vegetative growth and fruit production, offering a sustainable approach to improving crop performance.

plant biology↗

bioRxiv2025

The sympathoadrenal contribution to inferior vena cava formation

Vascular development is fundamental during embryogenesis. Although the molecular and cellular mechanisms of vascular formation have been extensively studied, the developmental basis common to anatomical variations in major veins remains poorly understood1-4. In particular, the renal segment of the inferior vena cava (IVC) exhibits marked anatomical variability, and these structural differences often affect the safety of retroperitoneal surgeries5,6. Here we show that the renal segment of the IVC in mouse embryos does not arise from the subcardinal vein (SubCV), as classically proposed7, but instead forms from a vascular plexus in the para-aortic ridge (PAR) closely associated with developing sympathetic and adrenal tissues. Three-dimensional imaging with molecular markers revealed the vascular plexus in PAR arises independently of the SubCV and develops in Zuckerkandl organ and adrenal gland primordia. Moreover, genetic models demonstrated that the development of the sympathetic and adrenal tissues contributes to the organization and remodeling of this vascular network. This sympathoadrenal contribution contrasts with the classical mesonephros-centric model and explains the consistent IVC structures observed even in the absence of renal development. Our findings suggest a mammal-specific mode of IVC formation driven by the emergence of dominant sympathetic paraganglia and reduced reliance on mesonephric filtration. This revised developmental framework provides insight into the evolutionary divergence of venous anatomy and may help interpret clinically significant vascular variations during abdominal surgery.

developmental biology↗

bioRxiv2025

MitoDelta: identifying mitochondrial DNA deletions at cell-type resolution from single-cell RNA sequencing data

BackgroundDeletion variants in mitochondrial DNA (mtDNA) are associated with various diseases, such as mitochondrial disorders and neurodegenerative diseases. Traditionally, mtDNA deletions have been studied using bulk DNA sequencing, but bulk methods average signals across cells, thereby masking the cell-type-specific mutational landscapes. Resolving mtDNA deletions at single-cell resolution is beneficial for understanding how these mutations affect distinct cell populations. To date, no specialized method exists for detecting cell-type-specific mtDNA deletions from single-cell RNA sequencing data. Notably, mtDNA possesses unique molecular features: a high copy number, stable transcription, and compact structure of the mitochondrial genome. This results in a relatively high abundance of mtDNA-derived reads even in single-cell RNA sequencing data, suggesting the possibility of detecting mtDNA deletion variants directly from transcriptomic data. ResultsHere, we present MitoDelta, a computational pipeline that enables the detection of mtDNA deletions at cell-type resolution solely from single-cell RNA sequencing data. MitoDelta combines a sensitive alignment strategy with robust statistical filtering based on a beta-binomial model, allowing accurate identification of deletion events even from noisy single-cell transcriptomes. To capture cell-type-specific deletion patterns, MitoDelta analyzes reads pooled by annotated cell types, enabling quantification of deletion burden across distinct cellular populations. We benchmarked MitoDelta against existing mtDNA deletion detection tools and demonstrated superior overall performance. As a practical application, we applied MitoDelta to a published single-nucleus RNA sequencing dataset for Parkinsons disease and revealed distinct mtDNA deletion burdens across neuronal subtypes. ConclusionsMitoDelta enables the transcriptome-integrated, cell-type-specific detection of mtDNA deletions from single-cell RNA sequencing data alone, offering a valuable framework for reanalyzing public datasets and studying mitochondrial genome alterations at cell-type resolution. This integrated approach enables insights into how mtDNA deletions are distributed across specific cell types and cellular states, providing new opportunities to investigate the role of mtDNA deletions in cell-type-specific disease mechanisms. The tool is available at https://github.com/NikaidoLaboratory/mitodelta.

bioinformatics↗

bioRxiv2023

Identification of a Musashi2 translocation as a novel oncogene in myeloid leukemia

Myeloid leukemias, diseases marked by aggressiveness and poor outcomes, are frequently triggered by oncogenic translocations. In the case of chronic myelogenous leukemia (CML) the BCR-ABL fusion initiates chronic phase disease with second hits allowing progression to blast crisis. Although Gleevec has been transformative for CML, blast crisis CML remains relatively drug resistant. Here we show that MSI2-HOXA9, a translocation with an unknown role in cancer, can serve as a second hit in driving bcCML. Compared to BCR-ABL, BCR-ABL/MSI2-HOXA9 led to a more aggressive disease in vivo with decreased latency, increased lethality and a differentiation blockade that is a hallmark of blast crisis. Domain mapping revealed that the MSI2 RNA binding domain RRM1 had a preferential impact on growth and lethality of bcCML relative to RRM2 or the HOXA9 domain. Mechanistically, MSI2-HOXA9 triggered global downstream changes with a preferential upregulation of mitochondrial components. Consistent with this, BCR-ABL/MSI2-HOXA9 cells exhibited a significant increase in mitochondrial respiration. These data suggest that MSI2-HOXA9 acts, at least in part, by increasing expression of the mitochondrial polymerase Polrmt and augmenting mitochondrial function and basal respiration in blast crisis. Collectively, our findings demonstrate for the first time that translocations involving the stem and developmental signal MSI2 can be oncogenic, and suggest that MSI, which we found to be a frequent partner for an array of translocations, could also be a driver mutation across solid cancers.

cancer biology↗

bioRxiv2022

Distinctiveness and continuity in transcriptome and connectivity in the anterior-posterior axis of the paraventricular nucleus of thalamus

The paraventricular nucleus of the thalamus (PVT) projects axons to multiple areas and mediates a wide range of behaviors. Heterogeneity of functions and axonal projections in PVT have been reported, but what cell types exist in PVT and how different they are have not been addressed. We applied single-cell RNA sequencing to depict transcriptomic characteristics of mouse PVT neurons. The transcriptome of PVT neurons had a continuous distribution with the largest variance corresponding to the anterior-posterior axis. Although the single-cell transcriptome classified PVT neurons into four types, transcriptomic and histological analyses showed their continuity. Similarly, anterior and posterior subpopulations had nearly non-overlapping axon projection patterns, while another population showed intermediate patterns. In addition, they responded differently to appetite-related neuropeptides, and their chemogenetic activation showed opposing effects in food consumption. Our studies showed contrasts and continuity of PVT neurons underlying their function as a behavior-modulating hub.

neuroscience↗

bioRxiv2019

Deletion of Stk11 and Fos in BLA projection neurons alters their intrinsic excitability and impairs formation of long-term aversive memory

Conditioned taste aversion (CTA) is a form of one-trial learning dependent on basolateral amygdala projection neurons (BLApn). Its underlying cellular and molecular mechanisms are poorly understood, however. We used RNAseq from BLApn to identify learning-related changes in Stk11, a kinase with well-studied roles in growth, metabolism and development, but not previously implicated in learning. Deletion of Stk11 restricted to BLApn completely blocks memory when occurring prior to training, but not following it, despite altering neither BLApn-dependent encoding of taste palatability in gustatory cortex, nor transcriptional activation of BLApn during training. Deletion of Stk11 in BLApn also increases their intrinsic excitability. Conversely, BLApn activated by CTA to express the immediate early gene Fos had reduced excitability. BLApn knockout of Fos also increased excitability and impaired learning. These data suggest that Stk11 and Fos expression play key roles in CTA long-term memory formation, perhaps by modulating the intrinsic excitability of BLApn.

neuroscience↗

bioRxiv2017

The Transcriptional Logic of Mammalian Neuronal Diversity

The mammalian nervous system is constructed of many cell types, but the principles underlying this diversity are poorly understood. To assess brain-wide transcriptional diversity, we sequenced the transcriptomes of the largest collection of genetically and anatomically identified neuronal classes. Using improved expression metrics that distinguish information content from signal-to-noise-ratio, we found that homeobox transcription factors contain the highest information about cell types and have the lowest noise. Genes that contribute the most to neuronal diversity tend to be long and enriched in factors specifically involved in neuronal function. Genome accessibility measurements reveal that long genes have more candidate regulatory elements arrayed in more distinct patterns. These elements frequently overlap interspersed repeats (mobile elements) and the pattern of repeats is predictive of gene expression. New regulatory sites resulting from elongation of neuronal genes by mobile elements may be an evolutionary force enhancing nervous system complexity.

neuroscience↗