Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1078586 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28026106_1.fastq.gz | Fastqsanger.gz | |||
| SRR28026106_2.fastq.gz | Fastqsanger.gz |
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Project description:Neuropathic pain is a highly prevalent condition for which treatments are hampered by low efficacy and dose-limiting side-effects. Injury to the somatosensory nervous system causes maladaptive plasticity that initiates and maintains chronic pain. Emerging evidence suggests that inflammatory cells of the innate immune system shape the injured nervous system and drive pain pathogenesis. Data from preclinical models and human patient biopsies have specifically implicated peripheral macrophage populations for a pro-algesic role, yet how these cell types influence damaged sensory neurons and whether they directly sensitise their neuronal activity is unclear. Here, we have developed an iPSC co-culture system to study the interactions of macrophages and sensory neurons in a fully humanised experimental model. We found that analogous to endogenous counterparts, iPSC-derived macrophages (iMacs) display a dynamic molecular and functional profile that is highly dependent on neuronal context. Co-culture with injured iPSC-derived sensory neurons (iSNs) induces morphological, gene expression, and secretory profile changes in iMacs that are consistent with in vivo nerve injury datasets. iMacs in turn amplify spontaneous firing in damaged sensory neurons, implicating macrophages in a cardinal feature of neuropathic pain. These results illustrate the utility of an iPSC-based model to study signalling between these two cell types; they support a role for macrophages in directly amplifying damaged sensory neuron activity and highlight disrupting pathological signalling between these cell types as a promising strategy for future analgesic drug development.
2025-05-28 | GSE298326 | GEO
Project description:Neuropathic pain is a highly prevalent condition for which treatments are hampered by low efficacy and dose-limiting side-effects. Injury to the somatosensory nervous system causes maladaptive plasticity that initiates and maintains chronic pain. Emerging evidence suggests that inflammatory cells of the innate immune system shape the injured nervous system and drive pain pathogenesis. Data from preclinical models and human patient biopsies have specifically implicated peripheral macrophage populations for a pro-algesic role, yet how these cell types influence damaged sensory neurons and whether they directly sensitise their neuronal activity is unclear. Here, we have developed an iPSC co-culture system to study the interactions of macrophages and sensory neurons in a fully humanised experimental model. We found that analogous to endogenous counterparts, iPSC-derived macrophages (iMacs) display a dynamic molecular and functional profile that is highly dependent on neuronal context. Co-culture with injured iPSC-derived sensory neurons (iSNs) induces morphological, gene expression, and secretory profile changes in iMacs that are consistent with in vivo nerve injury datasets. iMacs in turn amplify spontaneous firing in damage sensory neurons, implicating macrophages in a cardinal feature of neuropathic pain. These results illustrate the utility of an iPSC-based model to study signalling between these two cell types; supporting a role for macrophages in directly amplifying damaged sensory neuron activity and suggesting that disrupting pathological signalling between these cell types could be a fruitful avenue for analgesic drug development.
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Project description:Characterisation of iPSC derived Sensory neurons with Single Cell RNA-seq
| PRJNA778177 | ENA
Project description:Induced pluripotent stem cells (iPSCs) are a valuable resource for neurological disease-modeling and drug discovery, due to their ability to differentiate into neurons reflecting the genetics of the patient from which they are derived. iPSC-derived cultures, however, are highly variable due to differences in culture conditions. We investigated the effect of iPSC passage number on differentiation to optimize the generation of functional, mature sensory neurons (iPSC-dSNs). Three iPSC lines were differentiated into iPSC-dSNs at passage numbers within each of the following ranges: low (LP; 5-10), middle (MP; 20-26), and high (HP; 30-38). Morphology and pluripotency of the parent iPSCs were assessed prior to differentiation at each passage number. iPSC-dSNs were evaluated based on electrophysiological properties and expression of key neuronal markers. All iPSC lines displayed the same morphology and were similarly pluripotent across passage numbers. iPSC-dSNs were also morphologically comparable across passage numbers. However, the expression levels of neuronal markers and an analysis of sodium channel function indicated greater maturity in LP iPSC-dSNs. Our results demonstrate that lower passage numbers may be better suited for differentiation into peripheral sensory neurons. Further studies are warranted to elucidate factors that may contribute to the variability associated with iPSC passage number.
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Project description:Induced pluripotent stem cells (iPSCs) harbor great promise for in vitro generation of disease-relevant cell types, such as mesodiencephalic dopaminergic (mdDA) neurons involved in Parkinson’s disease. Although iPSC-derived midbrain DA neurons have been generated, detailed genetic and epigenetic characterization of such neurons is still lacking. The goal of this study is to examine the authenticity of iPSC-derived DA neurons obtained by established protocols. We FACS-purified mdDA (Pitx3gfp/+) neurons derived from mouse iPSCs and primary mdDA (Pitx3gfp/+) neurons to analyze and compare their genetic and epigenetic features. Although iPSC-derived DA neurons largely adopt characteristics of their in-vivo counterparts, relevant deviations in global gene expression and DNA methylation were found. Hypermethylated genes, mainly involved in neurodevelopment and basic neuronal functions, consequently showed reduced expression levels. Such abnormalities should be addressed as they might affect unambiguous long-term functionality and hamper the potential of iPSC-derived DA neurons for in-vitro disease modeling or cell-based therapy. RRBS methylation maps were generated for iPSCs cells, dopaminergic neurons derived from iPSCs and primary mesodiencephalic dopaminergic neurons
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Project description:Sensory neurons are nerve cells that are activated by sensory input such as heat, light and convey information to the brain. Although a key cell type in complex organisms, human sensory neurons are challenging to study because they are impossible to obtain from living donors. We have collaborated with the Neucentis Pharmaceutical Research Unit to differentiate sensory neuron like cells from human induced pluripotent stem cells derived as part of the Human Induced Pluripotent Stem Cells Initiative. We will sequence RNA from 100 IPS lines derived from healthy individuals and perform RNA-seq on the differentiated cells to identify noncoding variants that alter gene expression in human sensory neurons.
| EGAS00001001149 | EGA
Project description:Sensory neurons are nerve cells that are activated by sensory input such as heat, light and convey information to the brain. Although a key cell type in complex organisms, human sensory neurons are challenging to study because they are impossible to obtain from living donors. We have collaborated with the Neucentis Pharmaceutical Research Unit to differentiate sensory neuron like cells from human induced pluripotent stem cells derived as part of the Human Induced Pluripotent Stem Cells Initiative. We will sequence RNA from 100 IPS lines derived from healthy individuals and perform RNA-seq on the differentiated cells to identify noncoding variants that alter gene expression in human sensory neurons.
| EGAD00001003145 | EGA
Project description:sample 666823 and 666824 control IgG pulldown in human iPSC derived APPDp neurons
sample 666825 and 666826 TERT pulldown in human iPSC derived APPDp neurons
2021-10-05 | MSV000088190 | MassIVE
Project description:iPSC-derived motor neurons form sporadic ALS and Controls. 4 sALS iPSC lines and 4 Ctrl iPSC lines.
| EGAD00001008424 | EGA
Project description:iPSC-derived motor neurons form familial ALS and Controls. 2 fALS iPSC lines and 3 Ctrl iPSC lines.
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