scholarly journals Genome‐wide transcriptomic and proteomic studies of Rett syndrome mouse models identify common signaling pathways and cellular functions as potential therapeutic targets

2019 ◽  
Vol 40 (12) ◽  
pp. 2184-2196 ◽  
Author(s):  
Rahul Krishnaraj ◽  
Florencia Haase ◽  
Bronte Coorey ◽  
Edward J Luca ◽  
Ingar Wong ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Rett Syndrome ◽  
Mouse Models ◽  
Therapeutic Targets ◽  
Cellular Functions ◽  
Genome Wide

scholarly journals Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome

2013 ◽  
Vol 33 (34) ◽  
pp. 13612-13620 ◽  
Author(s):  
S. K. Garg ◽  
D. T. Lioy ◽  
H. Cheval ◽  
J. C. McGann ◽  
J. M. Bissonnette ◽  
...  
Keyword(s):  
Rett Syndrome ◽  
Mouse Models ◽  
Female Mouse ◽  
Systemic Delivery

Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences

2010 ◽  
Vol 41 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Pornrutsami Jintaridth ◽  
Apiwat Mutirangura
Keyword(s):  
Mononuclear Cells ◽  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cellular Functions ◽  
Peripheral Blood Mononuclear ◽  
Global Methylation ◽  
Short Interspersed Elements ◽  
Genome Wide ◽  
Age Dependent

Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = −0.452, P < 10−3) and HERV-K (r = −0.326, P < 10−3) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34–68 yr, and loss of methylation of HERV-K occurred during ages 40–63 yr and again during ages 64–83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10−3). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

Inositide-dependent signaling pathways as new therapeutic targets in myelodysplastic syndromes

2015 ◽  
Vol 20 (6) ◽  
pp. 677-687 ◽  
Author(s):  
Sara Mongiorgi ◽  
Carlo Finelli ◽  
Yong Ryoul Yang ◽  
Cristina Clissa ◽  
James A. McCubrey ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Myelodysplastic Syndromes ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

Rett syndrome treatment in mouse models: Searching for effective targets and strategies

2013 ◽  
Vol 68 ◽  
pp. 106-115 ◽  
Author(s):  
Laura Ricceri ◽  
Bianca De Filippis ◽  
Giovanni Laviola
Keyword(s):  
Rett Syndrome ◽  
Mouse Models

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals Elucidating the regulatory mechanism of Swi1 prion in global transcription and stress responses

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiqiang Du ◽  
Jeniece Regan ◽  
Elizabeth Bartom ◽  
Wei-Sheng Wu ◽  
Li Zhang ◽  
...  
Keyword(s):  
Stress Responses ◽  
Regulation Of Transcription ◽  
Interacting Proteins ◽  
Environmental Stress Response ◽  
Key Factors ◽  
Cellular Functions ◽  
Beneficial Effects ◽  
Genome Wide ◽  
Genes Encoding ◽  
A Subunit

AbstractTranscriptional regulators are prevalent among identified prions in Saccharomyces cerevisiae, however, it is unclear how prions affect genome-wide transcription. We show here that the prion ([SWI+]) and mutant (swi1∆) forms of Swi1, a subunit of the SWI/SNF chromatin-remodeling complex, confer dramatically distinct transcriptomic profiles. In [SWI+] cells, genes encoding for 34 transcription factors (TFs) and 24 Swi1-interacting proteins can undergo transcriptional modifications. Several TFs show enhanced aggregation in [SWI+] cells. Further analyses suggest that such alterations are key factors in specifying the transcriptomic signatures of [SWI+] cells. Interestingly, swi1∆ and [SWI+] impose distinct and oftentimes opposite effects on cellular functions. Translation-associated activities, in particular, are significantly reduced in swi1∆ cells. Although both swi1∆ and [SWI+] cells are similarly sensitive to thermal, osmotic and drought stresses, harmful, neutral or beneficial effects were observed for a panel of tested chemical stressors. Further analyses suggest that the environmental stress response (ESR) is mechanistically different between swi1∆ and [SWI+] cells—stress-inducible ESR (iESR) are repressed by [SWI+] but unchanged by swi1∆ while stress-repressible ESR (rESR) are induced by [SWI+] but repressed by swi1∆. Our work thus demonstrates primarily gain-of-function outcomes through transcriptomic modifications by [SWI+] and highlights a prion-mediated regulation of transcription and phenotypes in yeast.

scholarly journals A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets

2013 ◽  
Vol 20 (5) ◽  
pp. 1135-1145 ◽  
Author(s):  
Sophia Adamia ◽  
Benjamin Haibe-Kains ◽  
Patrick M. Pilarski ◽  
Michal Bar-Natan ◽  
Samuel Pevzner ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Rna Splicing ◽  
Myeloid Leukemia ◽  
Therapeutic Targets ◽  
Disease Markers ◽  
Genome Wide ◽  
A Genome ◽  
Aberrant Rna ◽  
Acute Myeloid
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