Gene expression profile at single cell level of immune cells from the dura mater of naïve C57BL6/N mice and during different phases of EAE.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278812 | GEO | 2024/12/20
REPOSITORIES: GEO
Dataset's files
| Action | DRS | |||
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| GSE278812_RAW.tar | Raw | |||
| GSE278812_harmony_integrated_all_sctransform.RData.gz | Rdata | |||
| GSE278812_harmony_integrated_naive_sctransform.RData.gz | Rdata | |||
| filelist.txt | Txt |
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Project description:Patient-derived cells hold great promise for precision medicine approaches in human health. Fibroblast cells have been a major source of human cells for reprogramming and differentiating into specific cell types for disease modeling. Such cells can be isolated at various stages during life (presymptomatic, symptomatic, and advanced disease) and thus can potentially be used to model different phases of disease progression. In certain circumstances, however, tissues are not collected during life and only postmortem tissues are the only available source of fibroblasts. Fibroblasts cultured from postmortem human dura mater of individuals with neurodegenerative diseases have been suggested as a primary source of cells for in vitro modeling of neurodegenerative diseases. Although fibroblast-like cells from human and mouse dura mater have been previously described, their utility for reprogramming and direct differentiation protocols requires further characterization. In this study, cells derived from dermal biopsies of living subjects were compared to cells derived from postmortem dura mater. In two instances, we have isolated and compared dermal and dural cell lines from the same subject. Notably, such striking differences were observed between cells of dermal and dural origin that their fibroblast nature was brought into question. Compared to dermal fibroblasts, postmortem dura mater-derived cells demonstrated different morphology, slower growth rates, and a higher rate of karyotype abnormality. Dura mater-derived cells also failed to express fibroblast protein markers. When dermal fibroblasts and dural-derived cells from the same subject were compared, they exhibited significant differences in gene expression profiles. Ultimately, dura mater-derived cells were found to originate from a mixed mural lineage consisting of smooth muscle cells and pericytes. Our study argues for rigorous karyotyping of all postmortem derived cell lines and highlights significant limitations of postmortem human dura mater-derived cells for modeling normal biology or disease-associated pathobiology.
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Project description:Background and purposeCalcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull.Experimental approachCGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20?min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres.Key resultsCapsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca(2+)-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca(2+)-free solutions. Olcegepant and CGRP(8-37) (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca(2+)-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater.Conclusion and implicationsWe have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine.
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