Gender-based blood transcriptomes and interactomes in multiple sclerosis: Involvement of SP1 dependent gene transcription

Menon, Ramesh; Dario, Marco Di; Cordiglieri, Chiara; Musio, Silvia; Mantia, L. La; Milanese, C.; Stefano, Anna Luisa Di; Crabbio, Massimo; Franciotta, Diego; Bergamaschi, Roberto; Pedotti, Rosetta; Medico, Enzo; Farina, Cinthia

doi:10.1016/j.jaut.2011.11.004

Cited by 41 publications

(29 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In fact, recent publications support similar sex differences in other immune related diseases, such as multiple sclerosis [43], and it is well established that autoimmune diseases are particularly prevalent in females [44]. All in all, therefore, these observations call for a careful exploration and re-analysis of available COPD genetic data by gender.…”

Section: Discussionmentioning

confidence: 75%

“…Here, a PCA of the expression values of those genes that show the largest variability across all experimental groups (COPD, S and NS) at baseline demonstrated a clear segregation of the leukocyte transcriptome profile by sex (Figure 2, Panel A). Hence, further statistical differential analyses were performed separately by gender, as previously described [24]. Figure 2 (Panels B1 and B2) presents the number of differentially expressed (DE) genes between T0 and T180 (red and green figures indicate up or down DE, respectively) in NS, S and COPD stratified by sex (Table S1 presents the complete list of DE genes).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

et al. 2014

View full text Add to dashboard Cite

BackgroundTobacco smoking is the main risk factor of chronic obstructive pulmonary disease (COPD) but not all smokers develop the disease. An abnormal pulmonary and systemic inflammatory response to smoking is thought to play a major pathogenic role in COPD, but this has never been tested directly.MethodsWe studied the systemic biomarker and leukocyte transcriptomic response (Affymetrix microarrays) to smoking exposure in 10 smokers with COPD and 10 smokers with normal spirometry. We also studied 10 healthy never smokers (not exposed to smoking) as controls. Because some aspects of COPD may differ in males and females, and the inflammatory response to other stressors (infection) might be different in man and women, we stratified participant recruitment by sex. Differentially expressed genes were validated by q-PCR. Ontology enrichment was evaluated and interaction networks inferred.ResultsPrincipal component analysis identified sex differences in the leukocyte transcriptomic response to acute smoking. In both genders, we identified genes that were differentially expressed in response to smoking exclusively in COPD patients (COPD related signature) or smokers with normal spirometry (Smoking related signature), their ontologies and interaction networks.ConclusionsThe use of an experimental intervention (smoking exposure) to investigate the transcriptomic response of peripheral leukocytes in COPD is a step beyond the standard case-control transcriptomic profiling carried out so far, and has facilitated the identification of novel COPD and Smoking expression related signatures which differ in males and females.

show abstract

Section: Discussionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

et al. 2014

View full text Add to dashboard Cite

show abstract

“…The raw data were background subtracted and cubic spine normalized using Illumina GenomeStudio software. Detection P-values reported by the GenomeStudio were used to estimate the amount of detected probes 51 , and a threshold of detection Pvalueo0.05 was applied for filtering. No outlier samples were found in principal component analysis and hierarchical sample clustering.…”

Section: Methodsmentioning

confidence: 99%

iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF

Laterza¹,

Merlini²,

Feo³

et al. 2013

Nat Commun

Self Cite

110

109

View full text Add to dashboard Cite

The possibility of generating neural stem/precursor cells (NPCs) from induced pluripotent stem cells (iPSCs) has opened a new avenue of research that might nurture bench-to-bedside translation of cell transplantation protocols in central nervous system myelin disorders. Here we show that mouse iPSC-derived NPCs (miPSC-NPCs)-when intrathecally transplanted after disease onset-ameliorate clinical and pathological features of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Transplanted miPSC-NPCs exert the neuroprotective effect not through cell replacement, but through the secretion of leukaemia inhibitory factor that promotes survival, differentiation and the remyelination capacity of both endogenous oligodendrocyte precursors and mature oligodendrocytes. The early preservation of tissue integrity limits blood-brain barrier damage and central nervous system infiltration of blood-borne encephalitogenic leukocytes, ultimately responsible for demyelination and axonal damage. While proposing a novel mechanism of action, our results further expand the therapeutic potential of NPCs derived from iPSCs in myelin disorders. T he development of cell-based therapies aimed at promoting remyelination in patients suffering from myelin disorders has been pursued in the last 30 years 1,2 . Although successful in supporting site-specific repair in focal myelin disease 3 , most of these cell-based therapeutic approaches have been mostly unsuccessful in multifocal inflammatory demyelinating diseases of the central nervous system (CNS), such as multiple sclerosis (MS).The recent demonstration that neural stem/precursor cell (NPCs)-based therapies can promote neuroprotection in experimental models of MS not only via cell replacement but also by secreting neuroprotective molecules-the so called bystander effect 4-7 -has suggested that such cells might represent in the near future a plausible alternative cell source for cell-based therapeutic strategy in MS. However, bench-to-bedside translation of NPC-based therapies in MS is still hampered by the allogenic nature of the so far only available source of NPCs for human trials. Indeed, although capable of promoting neuroprotection in a non-human primate model of MS 8 , fetalderived NPCs do require concomitant immunosuppression when transplanted in humans.Induced pluripotent stem cells (iPSCs)-a new source of pluripotent stem cells obtained by genetic reprogramming of somatic cells 9-11 -might represent the ideal autologous source of NPCs for transplantation and translational purposes in MS. However, although the ability of iPSC-derived myelin-forming cells (for example, OPCs) to remyelinate congenitally demyelinated mice has been recently shown 3 , nothing is known about the capacity of these cells to protect neural tissue once transplanted in an hostile inflammatory demyelinated environment such as that characterizing MS.Here we show that mouse iPSC-derived NPCs (thereafter referred as miPSC-NPCs)-when intrathecally transplanted after disease onset in m...

show abstract

“…In fact, MS is a multifactorial disorder determined by the complex interaction between genetic and environmental factors, whose integration occurs at the epigenetic level and determines gene expression. Our group has recently shown the importance of blood transcriptomics in uncovering gene expression changes and transcriptional regulators in MS. 5 In this study, we have (1) examined the expression levels of known MS susceptibility genes in peripheral blood mononuclear cells (PBMCs) of CIS, RR-MS, PP-MS, SP-MS, and control individuals, (2) identified a panel of blood transcriptional signatures for distinct MS forms, and (3) explored the pathways contributed by the dysregulated susceptibility genes.…”

mentioning

confidence: 99%

Dysregulation of MS risk genes and pathways at distinct stages of disease

Srinivasan

Dario

Russo

et al. 2017

Neurol Neuroimmunol Neuroinflamm

Self Cite

View full text Add to dashboard Cite

Objective:To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.Methods:We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.Results:Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage–specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.Conclusions:Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.

show abstract

Gender-based blood transcriptomes and interactomes in multiple sclerosis: Involvement of SP1 dependent gene transcription

Cited by 41 publications

References 55 publications

Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

Systemic Inflammatory Response to Smoking in Chronic Obstructive Pulmonary Disease: Evidence of a Gender Effect

iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF

Dysregulation of MS risk genes and pathways at distinct stages of disease

Contact Info

Product

Resources

About