Multi-modal single-cell sequencing identifies cellular immunophenotypes associated with juvenile dermatomyositis disease activity
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE190684 | GEO | 2022/04/30
REPOSITORIES: GEO
Similar Datasets
Project description:Multi-modal single-cell sequencing identifies cellular immunophenotypes associated with juvenile dermatomyositis disease activity
| PRJNA787953 | ENA
Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Experiment Overall Design: After obtaining informed consent, 23 girls with definite JDM were enrolled in this study prior to obtaining the MRI directed diagnostic muscle biopsy. All 23 JDM samples and 4 healthy age- and sex-matched controls were expression profiled and for first gene filtering. Only profiling data from untreated patients (19 profiles) were then analyzed statistically. Experiment Overall Design: disease duration : less than 2 months: YJD-JDM-2UA-s2,YJD-JDM-1UA-s2,YJD-JDM-16UA-s2 Experiment Overall Design: disease duration : more than 2 months:YJD-JDM-30UA-s2,YJD-JDM-19UA-s2,YJD-JDM-5UA-s2,YJD-JDM-21UA-s2,YJD-JDM-18UA-s2,YJD-JDM-3UA-s2,YJD-JDM-23UA-s2,YJD-JDM-9UA-S2,YJD-JDM-12UA-s2,YJD-JDM-14UA-s2,YJD-JDM-25UA-s2,YJD-JDM-8UA-s2,YJD-JDM-15UA-s2,YJD-JDM-13UA-s2,YJD-JDM-10UA-S2,YJD-JDM-6UA-s2.
2008-10-21 | E-GEOD-11971 | biostudies-arrayexpress
Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Keywords: Disease progression; time course
2008-07-18 | GSE11971 | GEO
Project description:RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.
2019-01-03 | E-MTAB-5616 | biostudies-arrayexpress
Project description:RNA sequencing was used to compare the transcriptional state of ex-vivo B-cells, moncytes and T-cells from children with Juvenile dermatomyositis (JDM) pre- and on-treatment and age-matched healthy controls. RNA was extracted from blood samples that were taken from juvenile dermatomyositis patients at diagnosis (before they received treatment) and approximately a year into treatment. The treatment included oral prednisolone, methotrexate, azathioprine, cyclophosphamide and other drugs.
2022-12-31 | GSE221091 | GEO
Project description:To better understand the pathogenesis of juvenile dermatomyositis (JDM) we examined the genetic alterations that result from exogenous IFN I exposure in pediatric skeletal muscle. We compared untreated healthy pediatric donor-derived myobundles with those treated with IFN I as well as with JAKi baricitinib and tofacitinib. We used bulk mRNA sequencing to evaluate how IFN I and treatment with JAKi influence healthy and JDM skeletal muscle gene expression and show IFNβ leads to a greater pro-inflammatory gene response than IFNα in pediatric skeletal muscle. As a type I interferon gene signature is established in JDM, downregulated oxidative phosphorylation, myogenesis, and contractile protein gene expression is implicated in JDM pathology. These genetic changes are partially reversed by JAK inhibitors, baricitinib and tofacitinib, with baricitinib leading to greater genetic alteration than tofacitinib. Our findings show that analysis of differential gene expression in bioengineered pediatric skeletal muscle can inform our knowledge of JDM pathogenesis and therapeutic effects.
2024-09-18 | GSE243339 | GEO
Project description:Juvenile dermatomyositis (JDM) is a rare autoimmune condition with insufficient biomarkers and treatments, in part, due to incomplete knowledge of the cell types mediating disease. We investigated immunophenotypes and cell-specific genes associated with disease activity using multiplexed RNA and protein single-cell sequencing applied to PBMCs from 4 treatment-naïve JDM (TN-JDM) subjects at baseline, 2, 4, and 6 months post-treatment and 4 subjects with inactive disease on treatment. Analysis of 55,564 cells revealed separate clustering of TN-JDM cells within monocyte, NK, CD8+ effector T and naïve B populations. The proportion of CD16+ monocytes was reduced in TN-JDM, and naïve B cells and CD4+ Tregs were expanded. Cell-type differential gene expression analysis and hierarchical clustering identified a pan-cell-type IFN gene signature over-expressed in TN-JDM in all cell types and correlated with disease activity most strongly in cytotoxic cell types. TN-JDM CD16+ monocytes expressed the highest IFN gene score and were highly skewed toward an inflammatory and antigen-presenting phenotype at both the transcriptomic and proteomic levels. A transitional B cell population with a distinct transcriptomic signature was expanded in TN-JDM and characterized by higher CD24 and CD5 proteins and less CD39, an immunoregulatory protein. This data provides new insights into JDM immune dysregulation at cellular resolution and serves as a novel resource for myositis investigators.
| S-EPMC9254730 | biostudies-literature
Project description:Skeletal muscle is highly vascularized. Beyond oxygen and nutriment supply, new functions for vessels have been recently identified, via the interactions that vessel cells establish with muscle progenitor cells. These latter cells closely interact with endothelial cells for their expansion and their differentiation, while periendothelial cells are involved in muscle cell self-renewal and return to quiescence. Thus, vessels play a central role in the tissue remodeling after an injury, while the mechanisms are poorly understood. We investigated myogenic/endothelial cell (MPCs/ECs) interactions in two paradigmatic contexts of regenerating muscle in the child: Juvenile Dermatomyositis (JDM), which is characterized by a transient loss of capillaries, and Duchenne Muscular Dystrophy (DMD), which is associated with an increase in vessel density. We showed in vitro specific interactions between myoblasts isolated from muscle of JDM and DMD patients and endothelial cells. In vitro myogenesis/angiogenesis studies demonstrated that MPCs exhibited various angiogenic properties depending on the pathological environment. In DMD, MPCs promoted the development of an anarchic, although strong, ECs stimulation, leading to the formation of weakly functional vessels. DMD cells presented an unbalanced homeostasis with nonspecific deregulation of several processes involved in muscle and vessel development. On the contrary, in JDM, MPCs enhanced the vessel reconstruction to efficiently restore the vessel function via the expression of a set of specific angiogenic effectors. MPCs exhibit a strong specific type I IFNs signature and ECs a dysregulation of their angiogenic capacities, suggesting a drastic reprogrammation of these cells in response to an inflammatory environment during JDM.
2017-07-27 | GSE66845 | GEO
Project description:Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA1*0501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21). Keywords: other
2003-07-16 | GSE493 | GEO
Project description:The goals of this study are to identify differentially expressed microRNAs in muscle between JDM and normal healthy controls, and to better understand the pathophysiology of JDM.
2016-06-06 | GSE49062 | GEO