Oxidative stress and impaired oligodendrocyte precursor cell differentiation in neurological disorders

Cellular and Molecular Life Sciences, Год журнала: 2021, Номер 78(10), С. 4615 - 4637

Опубликована: Март 10, 2021

Oligodendrocyte precursor cells (OPCs) account for 5% of the resident parenchymal central nervous system glial cells. OPCs are not only a back-up loss oligodendrocytes that occurs due to brain injury or inflammation-induced demyelination (remyelination) but also pivotal in plastic processes such as learning and memory (adaptive myelination). OPC differentiation into mature myelinating is controlled by complex transcriptional network depends on high metabolic mitochondrial demand. Mounting evidence shows dysfunction, culminating lack differentiation, mediates progression neurodegenerative disorders multiple sclerosis, Alzheimer's disease Parkinson's disease. Importantly, neurodegeneration characterised oxidative carbonyl stress, which may primarily affect plasticity demand limited antioxidant capacity associated with this cell type. The underlying mechanisms how oxidative/carbonyl stress disrupt remain enigmatic focus current research efforts. This review proposes role interfering changes required differentiation. In particular, oligodendrocyte (epi)genetics, cellular defence repair responses, signalling respiration, lipid metabolism represent key hamper disorders. Understanding impacts function pave way future OPC-targeted treatment strategies

Язык: Английский

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Spatially resolved epigenomic profiling of single cells in complex tissues

Cell, Год журнала: 2022, Номер 185(23), С. 4448 - 4464.e17

Опубликована: Окт. 21, 2022

The recent development of spatial omics methods has enabled single-cell profiling the transcriptome and 3D genome organization with high resolution. Expanding repertoire tools, a spatially resolved epigenomics method will accelerate understanding regulation cell tissue functions. Here, we report for epigenomic single cells using in situ tagmentation transcription followed by multiplexed imaging. We demonstrated ability to profile histone modifications marking active promoters, putative enhancers, silent promoters individual cells, generated high-resolution atlas hundreds enhancers embryonic adult mouse brains. Our results suggested promoter-enhancer pairs enhancer hubs regulating developmentally important genes. envision this approach be generally applicable epigenetic DNA-binding proteins, advancing our how gene expression is spatiotemporally regulated epigenome.

Язык: Английский

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Oncogenic functions and therapeutic targeting of EphA2 in cancer

Oncogene, Год журнала: 2021, Номер 40(14), С. 2483 - 2495

Опубликована: Март 8, 2021

Язык: Английский

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Single-cell DNA methylome and 3D multi-omic atlas of the adult mouse brain

Nature, Год журнала: 2023, Номер 624(7991), С. 366 - 377

Опубликована: Дек. 13, 2023

Cytosine DNA methylation is essential in brain development and implicated various neurological disorders. Understanding diversity across the entire a spatial context fundamental for complete molecular atlas of cell types their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) multi-omic (snm3C-seq)

Язык: Английский

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Genetics and Epigenetics of Human Pubertal Timing: The Contribution of Genes Associated With Central Precocious Puberty

Journal of the Endocrine Society, Год журнала: 2025, Номер 9(2)

Опубликована: Янв. 6, 2025

Abstract Human puberty is a dynamic biological process determined by the increase in pulsatile secretion of GnRH triggered distinct factors not fully understood. Current knowledge reveals fine tuning between an stimulatory and decrease inhibitory factors, where genetic epigenetic have been indicated as key players regulation onset lines evidence. Central precocious (CPP) results from premature reactivation GnRH. In past decade, identification causes CPP has largely expanded, revealing hypothalamic regulatory pubertal timing. Among them, 3 genes associated with are linked to mechanisms involving DNA methylation, reinforcing strong role epigenetics underlying this disorder. Loss-of-function mutations Makorin Ring-Finger Protein (MKRN3) Delta-Like Non-Canonical Notch Ligand 1 (DLK1), 2 autosomal maternally imprinted genes, described relevant monogenic phenotype exclusively paternal transmission. MKRN3 proven be component input on neurons through different mechanisms. Additionally, rare heterozygous variants Methyl-CpG-Binding (MECP2), X-linked gene that factor methylation machinery, were identified girls sporadic or without neurodevelopmental disorders. mini-review, we focus how revealed regulators human timing, summarizing latest associations MKRN3, DLK1, MECP2.

Язык: Английский

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Tregs: Where We Are and What Comes Next?

Frontiers in Immunology, Год журнала: 2017, Номер 8

Опубликована: Ноя. 24, 2017

Regulatory T cells are usually recognized as a specialized subset of CD4+ functioning in establishment and maintanence immune tolerance. Meanwhile, there is emerging evidence that Tregs also present various non-lymphoid tissues, they have unique phenotypes credited with activities distinct from regulatory function. Their development function been described plenty manuscripts the last two decades. However, deepening research recent years, revealed some novel mechanisms about how exert their activities. Firstly, we discuss expanding family lymphocytes briefly then, try to interpret Foxp3 functions. Subsequently, another part our focus varieties tissue Tregs. Next, primarily on work faceted functions terms soluble mediators, functional proteins inhibitory receptors. In particular, unless otherwise noted, term "Treg" used here refer specially "CD4+CD25+Foxp3+" cells.

Язык: Английский

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Transcriptional Regulation by Trithorax-Group Proteins

Cold Spring Harbor Perspectives in Biology, Год журнала: 2014, Номер 6(10), С. a019349 - a019349

Опубликована: Окт. 1, 2014

Robert E. Kingston1 and John W. Tamkun2 1Department of Molecular Biology, Massachusetts General Hospital, Boston, 02114 2Department Molecular, Cell Developmental University California, Santa Cruz, California 95064 Correspondence: kingston{at}molbio.mgh.harvard.edu

Язык: Английский

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Strategies for Targeting Gene Therapy in Cancer Cells With Tumor-Specific Promoters

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Дек. 14, 2020

Cancer is the second cause of death worldwide, surpassed only by cardiovascular diseases, due to lack early diagnosis, and high relapse rate after conventional therapies. Chemotherapy inhibits rapid growth cancer cells, but it also affects normal cells with fast proliferation rate. Therefore, imperative develop other safe more effective treatment strategies, such as gene therapy, in order significantly improve survival life expectancy patients cancer. The aim therapy transfect a therapeutic into host express itself beneficial biological effect. However, efficacy proposed strategies has been insufficient for delivering full potential clinic. type delivery vehicle (viral or non viral) chosen depends on desired specificity therapy. first trials were performed genes driven viral promoters CMV promoter, which induces non-specific toxicity tissues, addition cells. use tumor-specific over-expressed tumor, specific expression given increasing their localized activity. Several cancer- and/or systems have developed target This review aims provide up-to-date information concerning targeting including suppressor genes, suicide anti-tumor angiogenesis, silencing, gene-editing technology, well employed. Gene can be used complement traditional therapies treatments.

Язык: Английский

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Biophysical regulation of macrophages in health and disease

Journal of Leukocyte Biology, Год журнала: 2019, Номер 106(2), С. 283 - 299

Опубликована: Март 12, 2019

Abstract Macrophages perform critical functions for homeostasis and immune defense in tissues throughout the body. These innate cells are capable of recognizing clearing dead pathogens, orchestrating inflammatory healing processes that occur response to injury. In addition, macrophages involved progression many diseases including cardiovascular disease, fibrosis, cancer. Although it has long been known respond dynamically biochemical signals their microenvironment, role biophysical cues only recently emerged. Furthermore, involve also characterized by changes tissue environment. This review will discuss current knowledge about effects matrix stiffness, material topography, applied mechanical forces, on macrophage behavior. We describe molecules be important mechanotransduction, adhesion molecules, ion channels, as well nuclear mediators such transcription factors, scaffolding proteins, epigenetic regulators. Together, this illustrate a developing biology, speculate upon molecular targets may potentially exploited therapeutically treat disease.

Язык: Английский

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Exposure to the environmental endocrine disruptor TCDD and human reproductive dysfunction: Translating lessons from murine models

Reproductive Toxicology, Год журнала: 2016, Номер 68, С. 59 - 71

Опубликована: Июль 16, 2016

Язык: Английский

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