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Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells[chip_scRNAseq]

ABSTRACT: The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN. We integrated VSGOs with human colon organoids on a microfluidic device and applied this axis-on-a-chip model to Alzheimer's disease. Our results suggest that VSN could be a potential mediator for propagating gut-derived amyloid and tau to the brain in an APOE4- and LRP1-dependent manner. Furthermore, our approach was extended to include patient-derived iPS cells, which demonstrated a strong correlation with clinical data.

ORGANISM(S): Homo sapiens

PROVIDER: GSE271257 | GEO | 2024/07/19

REPOSITORIES: GEO

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Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells

Project description:The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN. We integrated VSGOs with human colon organoids on a microfluidic device and applied this axis-on-a-chip model to Alzheimer's disease. Our results suggest that VSN could be a potential mediator for propagating gut-derived amyloid and tau to the brain in an APOE4- and LRP1-dependent manner. Furthermore, our approach was extended to include patient-derived iPS cells, which demonstrated a strong correlation with clinical data.

2024-07-19 | GSE264303 | GEO

A molecular architecture of the vagal interoceptive system

Project description:Interoception, the ability to timely and precisely sense changes inside the body, is critical for survival. Vagal sensory neurons (VSNs) form an important body-to-brain axis, navigating along body’s rostral-caudal axis to their target organs and dive across organ’s surface-lumen axis into appropriate tissue layers to sense stimuli with various physical properties. The brain can discriminate numerous body signals through VSNs, yet the underlying molecular coding strategy remains poorly understood. Here we show that VSNs code visceral organ, tissue layer, and stimulus modality, three key features of an interoceptive signal, in different dimensions. Large-scale single-cell profiling of VSNs from seven major organs, including the lung, heart, stomach, esophagus, duodenum, pancreas, and transverse colon, using multiplexed projection-barcodes reveals a ‘visceral organ’ dimension composed of differentially expressed gene modules coding VSN target organs along body’s rostral-caudal axis. Surprisingly, we discover another ‘tissue layer’ dimension with gene modules coding VSN ending locations along organ’s surface-lumen axis. The three independent feature-coding dimensions together specify many parallel VSN pathways in a combinatorial fashion and facilitate complex VSN projection in the brainstem. Our study thus highlights a novel multidimensional coding architecture of the mammalian vagal interoceptive system for effective signal communication.

2022-01-07 | GSE192987 | GEO

Single-cell RNAseq Reveals Seven Classes of Visceral Sensory Neuron

Project description:Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. The principal neural unit in the bowel encoding these stimuli is the visceral sensory neuron with endings at the mucosa, intramurally and along mesenteric blood vessels. Sensory neurons activate reflex pathways and give rise to conscious sensation, however, the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by the current paucity of molecular markers. Here we overcome these limitations by comprehensive transcriptomic profiling and unsupervised clustering of single colonic sensory neurons revealing 7 classes characterised from both lumbar splanchnic (LSN) and pelvic nerves (PN). We identify and classify neurons based on novel marker genes, confirm translation of patterning to protein expression and show subtype-selective differential agonist activation, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity.

2018-02-27 | GSE102962 | GEO

Effect of LRP1 deletion in vascular mural cells and APOE gentotype on gene expression in mouse brains

Project description:To investigate the apoE isoform-dependent role of vascular mural cell (VMC)-LRP1, we generated VMC-specific LRP1 knockout mice (smLrp1-/-), followed by breeding these mice with either APOE3-targeted replacement (TR) or APOE4-TR mice We then performed gene expression profiling analysis using data obtained from RNA-seq of cortical samples from 4 different mouse models

2023-05-12 | GSE225065 | GEO

Ontogeny and Trophic Factor Sensitivity of Gastrointestinal Projecting Vagal Sensory Cell Types

Project description:Vagal sensory neurons (VSNs) located in the nodose ganglion provide information, such as stomach stretch or the presence of ingested nutrients, to the caudal medulla via specialized cell types expressing unique marker genes. Here, we leverage VSN marker genes identified in adult mice to determine when specialized vagal subtypes arise developmentally and the trophic factors that shape their growth. Experiments to screen for trophic factor sensitivity revealed that brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) robustly stimulate neurite outgrowth from VSNs in vitro. Perinatally, BDNF was expressed by neurons of the nodose ganglion itself, while GDNF was expressed by intestinal smooth muscle cells. Thus, BDNF may support VSNs locally, whereas GDNF may act as a target-derived trophic factor supporting the growth of processes at distal innervation sites in the gut. Consistent with this, expression of the GDNF receptor was enriched in VSN cell types that project to the gastrointestinal tract. Lastly, mapping of genetic markers in the nodose ganglion demonstrates that defined vagal cell types begin to emerge as early as embryonic day 13, even as VSNs continue to grow to reach gastrointestinal targets. Despite the early onset of expression for some marker genes, expression patterns of many cell type markers appear immature in prenatal life and mature considerably by the end of the first postnatal week. Together, the data support location-specific roles for BDNF and GDNF in stimulating VSN growth, and a prolonged perinatal timeline for VSN maturation in male and female mice.

2023-03-21 | GSE227845 | GEO

Transcription profiling of nodose or dorsal root ganglion visceral sensory neurons from mice infected with N. brasiliensis and/or subjected to environmental stress to determine molecular signatures for post-infective visceral chemosensitivity associated with irritable bowel syndrome

Project description:Background & Aims: Visceral hypersensitivity, a hallmark of irritable bowel syndrome, is generally considered to be mechanosensitive in nature and mediated via spinal afferents. Both stress and inflammation are implicated in visceral hypersensitivity, but the underlying molecular mechanisms of visceral hypersensitivity are unknown. <br> Methods: Mice were infected with Nippostrongylus brasiliensis (Nb) larvae, exposed to environmental stress and the following separate studies performed 3-4 weeks later. Mesenteric afferent nerve activity was recorded in response to either ramp balloon distension (60 mmHg), or to an intraluminal perfusion of hydrochloric acid (50 mM), or to octreotide administration (2 µM). Intraperitoneal injection of cholera toxin B-488 identified neurons projecting to the abdominal viscera. Fluorescent neurons in dorsal root and nodose ganglia were isolated using laser-capture microdissection. RNA was hybridised to Affymetrix Mouse whole genome arrays for analysis to evaluate the effects of stress and infection. <br> Results: In mice previously infected with Nb, there was no change in intestinal afferent mechanosensitivity, but there was an increase in chemosensitive responses to intraluminal hydrochloric acid when compared to control animals. Gene expression profiles in vagal but not spinal visceral sensory neurons were significantly altered in stressed Nb-infected mice. Decreased afferent responses to somatostatin receptor 2 stimulation correlated with lower expression of vagal somatostatin receptor 2 in stressed Nb-infected mice, confirming a link between molecular data and functional sequelae. <br> Conclusions: Alterations in the intestinal brain-gut axis, in chemosensitivity but not mechanosensitivity, and through vagal rather than spinal pathways, are implicated in stress-induced post-inflammatory visceral hypersensitivity.

2008-01-31 | E-JJRD-1 | biostudies-arrayexpress

Enteroendocrine cell lineages that differentially control feeding and gut motility

Project description:Enteroendocrine cells (EECs) are specialized sensory cells of the gut-brain axis that are sparsely distributed along the intestinal epithelium.

2023-02-21 | GSE224223 | GEO

Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells

Project description:Differentiating visceral sensory ganglion organoids from induced pluripotent stem cells

| PRJNA1101932 | ENA

Microglia gravitate toward amyloid plaques surrounded by externalized phosphatidylserine via TREM2

Project description:iPSC-derived brain organoids with microglial cells (assembloids) were used for this study. We used single cell RNA sequencing (scRNA-seq) to analyze the difference between APOE3 and APOE4 genotypes

2023-09-01 | GSE220690 | GEO

Expression of receptors for inflammatory mediators in murine vagal nodose versus jugular capsaicin-sensitive (Trpv1-positive) C-fiber neurons

Project description:Capsaicin-sensitive (Trpv1-positive) sensory C-fibers derived from vagal ganglia innervate the visceral organs, and respond to inflammatory mediators and noxious stimuli. These neurons play an important role in maintenance of visceral homeostasis, and contribute to the symptoms of visceral inflammatory diseases. Vagal sensory neurons are located in two ganglia, the jugular ganglia (derived from the neural crest), and the nodose ganglia (from the epibranchial placodes). The functional difference, especially in response to immune mediators, between jugular and nodose neurons is not fully understood. In this study, we microscopically isolated murine nodose and jugular capsaicin-sensitive / Trpv1-expressing C-fiber neurons and performed transcriptome profiling using ultra-low input RNA sequencing.

2017-10-01 | GSE102123 | GEO

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