Publisher Correction: Dynamics of oligodendrocyte generation in multiple sclerosis

Yeung, Maggie S. Y.; Djelloul, Mehdi; Steiner, Embla; Bernard, Samuel; Salehpour, Mehran; Possnert, Göran; Brundin, Lou; Frisén, Jonas

doi:10.1038/s41586-019-0935-7

Cited by 10 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A complex picture can be depicted in which ERs may interact with genomic regulatory regions to recruit coregulators and chromatin remodelers. The NGS approach could pave the way to a deeper knowledge of the gene expression and regulation involved in these cell dynamics, as shown in recent studies that have explored MS brain lesions at single-cell resolution [159,160,161].…”

Section: Discussionmentioning

confidence: 99%

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Maglione

Rolla

Mercanti

et al. 2019

Cells

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic central nervous system inflammatory disease that leads to demyelination and neurodegeneration. The third trimester of pregnancy, which is characterized by high levels of estrogens, has been shown to be associated with reduced relapse rates compared with the rates before pregnancy. These effects could be related to the anti-inflammatory properties of estrogens, which orchestrate the reshuffling of the immune system toward immunotolerance to allow for fetal growth. The action of these hormones is mediated by the transcriptional regulation activity of estrogen receptors (ERs). Estrogen levels and ER expression define a specific balance of immune cell types. In this review, we explore the role of estradiol (E2) and ERs in the adaptive immune system, with a focus on estrogen-mediated cellular, molecular, and epigenetic mechanisms related to immune tolerance and neuroprotection in MS. The epigenome dynamics of immune systems are described as key molecular mechanisms that act on the regulation of immune cell identity. This is a completely unexplored field, suggesting a future path for more extensive research on estrogen-induced coregulatory complexes and molecular circuitry as targets for therapeutics in MS.

show abstract

Section: Discussionmentioning

confidence: 99%

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Maglione

Rolla

Mercanti

et al. 2019

Cells

View full text Add to dashboard Cite

show abstract

“…The stimulation of remyelination has been proposed to restore neurological function and prevent neurodegeneration in regions of chronic demyelination. Although spared oligodendrocytes (OLs) may contribute to remyelination in MS and in some experimental models (Yeung et al, 2019, Duncan et al, 2018, Bacmeister et al, 2020), when large numbers of adult OLs are destroyed remyelination relies on the generation of new OLs by oligodendrocyte progenitor cells (OPCs) (Hughes et al, 2013, Zawadzka et al, 2010). The cellular processes of remyelination can be broadly divided into recruitment and differentiation phases (Franklin and Ffrench-Constant, 2017).…”

Section: Introductionmentioning

confidence: 99%

Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation

Cooper

Polanco

Saraswat

et al. 2022

Preprint

View full text Add to dashboard Cite

Remyelination-inducing therapies have the potential to restore neurologic function and prevent progression in multiple sclerosis (MS). However, preclinical therapies capable of driving oligodendrocyte differentiation and enhancing remyelination in murine models have not yet yielded meaningful clinical improvement. These setbacks suggest that small animal models may be inadequate for the development and identification of promising regenerative therapies. Unlike MS, rodent models of demyelination undergo highly efficient remyelination, have typically very small volumes and exhibit abundant oligodendrocyte recruitment rapidly following demyelination. We hypothesized that oligodendrocyte progenitor cell (OPC) recruitment becomes rate-limiting as lesion volume increases leading to a failure of oligodendrocyte differentiation and endogenous remyelination. In this study, we utilized lysolecithin injection into the large white matter tracts of the rabbit to create demyelinated lesions that have cross-sectional areas 20-fold larger than those previously reported in mice, and volumes 8-fold larger. Unlike rodent lesions which show robust supernumerary OPC recruitment (representing a 3-10 fold increase in Olig2+ cell density), recruitment in the rabbit never exceeds normal levels. Importantly, the density of mature CC1+ oligodendrocytes failed to return to NAWM levels by 56 dpl and the percentage of differentiated oligodendrocytes drastically lagged behind that of rodent lesions. These results suggest that as lesion volume increases the requirement for increased OPC proliferation and migration becomes limiting. As oligodendrocyte differentiation from human OPCs is dependent on the local density of progenitors, the reduced density of progenitors in large lesions may contribute to failed differentiation and remyelination. Together, we show that large volume demyelination in the white matter of the rabbit recapitulates several key features of human MS lesions, and represents an important preclinical model for the assessment of remyelination therapies in human demyelinating disease.

show abstract

Section: Introductionmentioning

confidence: 99%

“…[8] The overproduction of inflammatory factors damages oligodendrocytes, causing their necrosis and apoptosis, with subsequent shedding of myelin sheaths. [9] In the pathogenesis of MS, the immune system and glial cell proliferation play a major role in disease progression. [10] MicroRNAs (miRNAs), a class of endogenous noncoding RNAs, are generally only 18-25 bp in length and are mostly small-molecule single-stranded RNAs.…”

Section: Introductionmentioning

confidence: 99%

“…This suggests that Th1 and Th17 cells in the peripheral immune system and the inflammatory factors they secrete are the main cause of MS disease progression [8] . The overproduction of inflammatory factors damages oligodendrocytes, causing their necrosis and apoptosis, with subsequent shedding of myelin sheaths [9] . In the pathogenesis of MS, the immune system and glial cell proliferation play a major role in disease progression [10] …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of key genes and microRNAs for multiple sclerosis using bioinformatics analysis

Feng

Zhu

et al. 2021

Medicine

View full text Add to dashboard Cite

To better understand the molecular mechanism underlying the pathogenesis of multiple sclerosis (MS), we aimed to identify the key genes and microRNAs (miRNA) associated with MS and analyze their interactions. Differentially expressed genes (DEGs) and miRNAs (DEMs) based on the gene miRNA dataset GSE17846 and mRNA dataset GSE21942 were determined using R software. Next, we performed functional enrichment analysis and constructed a protein–protein interaction network. Data validation was performed to ensure the reliability of hub genes. The miRNA-mRNA regulatory network was constructed. In total, 47 DEMs and 843 DEGs were identified. Protein–protein interaction network analysis identified several hub genes, including JUN, FPR2, AKT1, POLR2L, LYZ, CXCL8, HBB, CST3, CTSZ, and MMP9 , especially LYZ and CXCL8 . We constructed an miRNA-mRNA regulatory network and found that hsa-miR-142-3p, hsa-miR-107, hsa-miR-140-5p, and hsa-miR-613 were the most important miRNAs. This study reveals some key genes and miRNAs that may be involved in the pathogenesis of MS, providing potential targets for the diagnosis and treatment of MS.

show abstract

Publisher Correction: Dynamics of oligodendrocyte generation in multiple sclerosis

Cited by 10 publications

References 0 publications

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

The Adaptive Immune System in Multiple Sclerosis: An Estrogen-Mediated Point of View

Chronic demyelination of rabbit lesions is attributable to failed oligodendrocyte progenitor cell repopulation

Identification of key genes and microRNAs for multiple sclerosis using bioinformatics analysis

Contact Info

Product

Resources

About