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Ishishita, S.

Publications and source records attributed to Ishishita, S..

3 recordsLinked to original sources

Deep Cellular and Spatial Profiling of the Mouse Spinal Cord Reveals Sex-Specific Neuron Types and the Ascending Projection Neuron Repertoire

The spinal cord gives rise to central somatosensation and orchestrates autonomic and motor control. How its cellular diversity achieves functions across sex, longitudinal axis and links the spinal cord to the brain remains poorly understood. Here we used retrograde viral tracing with spatial transcriptomics and multiomic profiling of over 750,000 mouse spinal cord neurons to define its output logic and functional cellular repertoire. We identified 78 ascending spinal projection neuron classes that link it to hind-, mid-, and forebrain centers for itch, touch, and pain revealing its output wiring logic. Furthermore, we characterized >500 anatomically and transcriptomically distinct neuron types with extensive ([~]55%) rostro-caudal specialization as well as first sex specific spinal neurons. Finally, we assembled a cell-type-to-phenotype map of spinal output neurons based on genetically defined interventions. Consequently, we deliver an anatomically and functionally annotated atlas of the adult mouse spinal cord to guide future interrogation of the organ.

neuroscience↗

A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences

The spinal cord is the gateway for somatosensory and nociceptive information to the brain and a key locus for sensory-motor integration. Studies in mice have advanced our understanding of spinal cord circuitry, and transcriptomic studies have begun to characterize the human spinal cord; however, major gaps in knowledge persist. We conducted single-nucleus sequencing of lumbar spinal cord tissue from 11 adult organ donors and annotated spinal cord cell types with high resolution spatial transcriptomics. We identified 34 spatially and transcriptionally defined neuronal classes and detected sex-specific cell types and states across multiple glial populations. Electrophysiological recordings from dorsal horn neurons revealed firing patterns for neuronal subtypes and group I mGluR-dependent plasticity. Our work defines previously unknown aspects of human spinal cord molecular anatomy and physiology.

neuroscience↗

Uterus-specific transcriptional regulation underlies eggshell pigment production in Japanese quail

The precursor of heme, protoporphyrin IX (PPIX), accumulates abundantly in the uterus of birds, such as Japanese quail, Coturnix japonica, resulting in brown-speckled eggshells. The molecular basis of PPIX production in the uterus remains largely unknown. Here, we investigated the cause of low PPIX production in a classical Japanese quail mutant exhibiting white eggshells by comparing its gene expression in the uterus with that of the wild type using transcriptome analysis and performed genetic linkage mapping to identify the causative genomic region of the white eggshell phenotype. We showed that 11 genes, including the 5-aminolevulinic acid synthase 1 (ALAS1) and ferroxidase hephaestin-like 1 (HEPHL1) genes, were specifically upregulated in the wild-type uterus and downregulated in the mutant. We mapped the 172 kb candidate genomic region on chromosome 6, which contains several genes, including a part of the paired-like homeodomain 3 (PITX3), which encodes a transcription factor. ALAS1, HEPHL1, and PITX3 were expressed in the apical cells of the luminal epithelium and lamina propria cells of the uterine mucosa of the wild-type quail, and their expression was downregulated in these cells of the mutant quail. Biochemical analysis using uterine homogenates indicated that the restricted availability of 5-aminolevulinic acid is the main cause of low PPIX production. These results suggest that uterus-specific transcriptional regulation of heme-biosynthesis-related genes is an evolutionarily acquired mechanism of eggshell pigment production in Japanese quail.

genetics↗