Novel gene expression profile of women with intrinsic skin youthfulness by transcriptome sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE85861 | GEO | 2016/12/16
SECONDARY ACCESSION(S): PRJNA339576
REPOSITORIES: GEO
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Project description:Aims: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi receptor tyrosine kinase inhibitor (TKI), has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored. Methods and Results: We performed lncRNA expression profiling to identify potential lncRNAs that are dysregulated in human induced pluripotent stem cells-derived ECs (iPSC-ECs) treated with sunitinib. We show that the lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) is significantly diminished in sunitinib-treated iPSC-ECs. Sunitinib was found to downregulate HAS2-AS1 by an epigenetic mechanism involving hypermethylation. Depletion of HAS2-AS1 recapitulated sunitinib-induced detrimental effects on iPSC-ECs, whereas CRISPR-mediated activation of HAS2-AS1 reversed sunitinib-induced dysfunction. We confirm that HAS2-AS1 stabilizes the expression of its sense gene HAS2 via an RNA/mRNA heteroduplex formation. Knockdown of HAS2-AS1 led to reduced synthesis of hyaluronic acid (HA) and upregulation of ADAMTS5, an enzyme involved in extracellular matrix degradation, resulting in disruption of the endothelial glycocalyx which is critical for ECs. In vivo, sunitinib-treated mice showed reduced coronary flow reserve, accompanied by a reduction in has2os and degradation of the endothelial glycocalyx. Finally, we identify that treatment with high molecular-weight HA can prevent the deleterious effects of sunitinib both in vitro and in vivo by preserving the endothelial glycocalyx. Conclusions: Our findings highlight the importance of lncRNA-mediated regulation of the endothelial glycocalyx as an important determinant of sunitinib-induced vascular toxicity and reveal potential novel therapeutic avenues to attenuate sunitinib-induced vascular dysfunction.
2023-04-30 | GSE216453 | GEO
Project description:Aims: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi receptor tyrosine kinase inhibitor (TKI), has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored. Methods and Results: We performed lncRNA expression profiling to identify potential lncRNAs that are dysregulated in human induced pluripotent stem cells-derived ECs (iPSC-ECs) treated with sunitinib. We show that the lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) is significantly diminished in sunitinib-treated iPSC-ECs. Sunitinib was found to downregulate HAS2-AS1 by an epigenetic mechanism involving hypermethylation. Depletion of HAS2-AS1 recapitulated sunitinib-induced detrimental effects on iPSC-ECs, whereas CRISPR-mediated activation of HAS2-AS1 reversed sunitinib-induced dysfunction. We confirm that HAS2-AS1 stabilizes the expression of its sense gene HAS2 via an RNA/mRNA heteroduplex formation. Knockdown of HAS2-AS1 led to reduced synthesis of hyaluronic acid (HA) and upregulation of ADAMTS5, an enzyme involved in extracellular matrix degradation, resulting in disruption of the endothelial glycocalyx which is critical for ECs. In vivo, sunitinib-treated mice showed reduced coronary flow reserve, accompanied by a reduction in has2os and degradation of the endothelial glycocalyx. Finally, we identify that treatment with high molecular-weight HA can prevent the deleterious effects of sunitinib both in vitro and in vivo by preserving the endothelial glycocalyx. Conclusions: Our findings highlight the importance of lncRNA-mediated regulation of the endothelial glycocalyx as an important determinant of sunitinib-induced vascular toxicity and reveal potential novel therapeutic avenues to attenuate sunitinib-induced vascular dysfunction.
2023-04-30 | GSE216452 | GEO
Project description:Investigation of Gene Expression Profiling in Unstaged Head Hair Follicles Plucked from Men and Women Experiment Overall Design: Total RNA was extracted from 1-3 unstaged follicles plucked from the scalp of each of 36 adult human volunteers. The average quantifiable yield of RNA per follicle was 112.5 ng. Ten samples were selected, based on ribosomal ratio, relative integrity number and total yield, for expression profiling. By preamplifying the extracted RNA (starting with as little as 30 ng), sufficient labeled RNA was generated to conduct Afymetrix-based gene expression analysis.
2007-12-11 | E-GEOD-3058 | biostudies-arrayexpress
Project description:Experiments were designed to evaluate changes in the transcriptome (mRNA levels) in the ovulatory, luteinizing follicle of rhesus monkeys, using a controlled ovulation (COv) model that permits analysis of the naturally selected, dominant follicle at specific intervals (0, 12, 24, 36 hours) after exposure to an ovulatory (exogenous hCG) stimulus during the menstrual cycle. Total RNA was prepared from individual follicles (n=4-8/timepoint), with an aliquot used for microarray analysis (AffymetrixTM Rhesus Macaque Genome Array) and the remainder applied to quantitative real-time PCR (q-PCR) assays. The microarray data from individual samples distinctly clustered according to timepoints, and ovulated follicles displayed markedly different expression patterns from unruptured follicles at 36 h. Between timepoint comparisons revealed profound changes in mRNA expression profiles. The dynamic pattern of mRNA expression for steroidogenic enzymes (CYP17A, CYP19A, HSD3B2, HSD11B1, HSD11B2), StAR, and gonadotropin receptors (LHCGR, FSHR) as determined by microarray analysis correlated precisely with those from blinded q-PCR assays. Patterns of mRNA expression for EGF-like factors (AREG, EREG) and processes (HAS2, TNFAIP6) implicated in cumulus-oocyte maturation/expansion were also comparable between assays. Thus, several mRNAs displayed the expected expression pattern for purported theca (e.g., CYP17A, AREG), granulosa (CYP19A, FSHR), cumulus (HAS2, TNFAIP6) cell, and surface epithelium (HSD11B) related genes in the rodent/primate preovulatory follicle. This database will be of great value in analyzing molecular and cellular pathways associated with periovulatory events in the primate follicle (e.g. follicle rupture, luteinization, inflammatory response, and angiogenesis), and for identifying novel gene products controlling mammalian fertility. Keywords: time course Total RNA was prepared from individual follicles (n=4-8/timepoint). Dominant follicles were selected specific intervals (0, 12, 24, 36 hours) after exposure to an ovulatory (exogenous hCG) stimulus during the menstrual cycle.
2011-02-15 | E-GEOD-22776 | biostudies-arrayexpress
Project description:We established a culture method of human keratinocytes from the bulge region of a plucked hair follicle, that contains multipotent epithelial stem cells with high proliferative potential. Using our method, keratinocyte cultures were successfully obtained from all subjects without invasive skin biopsies. We compared the gene expression profiles between the cultured keratinocytes derived from human hair-follicle-bulge (bulgeM-bM-^@M-^Sderived keratinocytes; BDKs) and neonatal human epidermal keratinocytes (NHEKs), and between BDKs from donors with atopic dermatitis and non-atopic controls using microarray analysis. Keywords: expressin profiling Two cell cultures, BDK vs. NHEK cells. 18 BDKs; derived from eighteen healthy volunteers , 6 NHEKs; purchased from Kurabo (Osaka, Japan). One replicate per array.
2013-02-05 | E-GEOD-13709 | biostudies-arrayexpress
Project description:Experiments were designed to evaluate changes in the transcriptome (mRNA levels) in the ovulatory, luteinizing follicle of rhesus monkeys, using a controlled ovulation (COv) model that permits analysis of the naturally selected, dominant follicle at specific intervals (0, 12, 24, 36 hours) after exposure to an ovulatory (exogenous hCG) stimulus during the menstrual cycle. Total RNA was prepared from individual follicles (n=4-8/timepoint), with an aliquot used for microarray analysis (AffymetrixTM Rhesus Macaque Genome Array) and the remainder applied to quantitative real-time PCR (q-PCR) assays. The microarray data from individual samples distinctly clustered according to timepoints, and ovulated follicles displayed markedly different expression patterns from unruptured follicles at 36 h. Between timepoint comparisons revealed profound changes in mRNA expression profiles. The dynamic pattern of mRNA expression for steroidogenic enzymes (CYP17A, CYP19A, HSD3B2, HSD11B1, HSD11B2), StAR, and gonadotropin receptors (LHCGR, FSHR) as determined by microarray analysis correlated precisely with those from blinded q-PCR assays. Patterns of mRNA expression for EGF-like factors (AREG, EREG) and processes (HAS2, TNFAIP6) implicated in cumulus-oocyte maturation/expansion were also comparable between assays. Thus, several mRNAs displayed the expected expression pattern for purported theca (e.g., CYP17A, AREG), granulosa (CYP19A, FSHR), cumulus (HAS2, TNFAIP6) cell, and surface epithelium (HSD11B) related genes in the rodent/primate preovulatory follicle. This database will be of great value in analyzing molecular and cellular pathways associated with periovulatory events in the primate follicle (e.g. follicle rupture, luteinization, inflammatory response, and angiogenesis), and for identifying novel gene products controlling mammalian fertility. Keywords: time course
2011-02-15 | GSE22776 | GEO
Project description:The human hair follicle bulge is an important niche for keratinocyte stem cells (KSCs). Elucidation of human bulge cell biology could be facilitated by analysis of global gene expression profiles and identification of unique cell-surface markers. The lack of distinctive bulge morphology in human hair follicles has hampered studies of bulge cells and KSCs. In this study, we determined the distribution of label-retaining cells to define the human anagen bulge. Using navigated laser capture microdissection, bulge cells and outer root sheath cells from other follicle regions were obtained and analyzed with cDNA microarrays. Gene transcripts encoding inhibitors of WNT and activin/bone morphogenic protein signaling were overrepresented in the bulge, while genes responsible for cell proliferation were underrepresented, consistent with the existence of quiescent noncycling KSCs in anagen follicles. Positive markers for bulge cells included CD200, PHLDA1, follistatin, and frizzled homolog 1, while CD24, CD34, CD71, and CD146 were preferentially expressed by non-bulge keratinocytes. Importantly, CD200+ cells (CD200hiCD24loCD34loCD71loCD146lo) obtained from hair follicle suspensions demonstrated high colony-forming efficiency in clonogenic assays, indicating successful enrichment of living human bulge stem cells. The stem cell behavior of enriched bulge cells and their utility for gene therapy and hair regeneration will need to be assessed in in vivo assays.
2007-11-08 | E-GEOD-3419 | biostudies-arrayexpress
Project description:Background: HAS2 is a member of the gene family encoding hyaluronan synthase 2 (HAS2) which can generate high molecular weight hyaluronan (HMW-HA). Although we previously reported that HAS2 is a novel candidate gene for susceptibility to adult asthma., little is known about whether HAS2 dysfunction affect eosinophilic airway inflammation. Objective: We therefore hypothesized that attenuation of HAS2 will enhance eosinophilic airway inflammation. Methods: C57BL/6 wild type (WT) mice, Has2 heterozygous deficient (Has2+/−) mice were used in eosinophilic airway inflammation model which induced by ovalbumin (OVA). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to detect Has2 and HA binding protein mRNA expression levels. Lung tissue and lavage fluid (BALF) were analyzed for inflammation and various cytokines and chemokines. Airway resistance was measured using forced oscillation technique. gene expression analyses were also performed to elucidate further pathogenesis. Results: The expression levels of Has2 mRNA was significantly decreased in OVA stimulated Has2+/− (Has2+/−-OVA) mice. Has2+/−-OVA mice also displayed significant reduce of CD44, and TGF-beta1 mRNA expression. BALF eosinophil number, levels of various Th2 cytokines and chemokines in BALF, and airway responsiveness were significantly increased in Has2+/−-OVA mice compared with similarly treated WT mice. ILK Signaling and PKA signaling were downregulated significantly more in Has2+/−-OVA mice compared with similarly treated WT mice. Conclusions: Has2 dysfunction induce more intense allergic eosinophilic airway inflammation and increase of airway hyper responsiveness with impairment of HAS2-CD44-TGF-beta signaling. Modulating HAS2 signaling might provide novel therapeutic targets for intractable bronchial asthma patients.
2022-04-04 | GSE148161 | GEO
Project description:Analysis of hepatic stellate cells (HSCs) isoltaed from ASMA-HAS2 transgenic and HSC-specific Has2 knockout mice. HAS2 synthesized hyaluronic acid, one of major extracellular matrix. Results provide insight into the role of HAS2 in hepatic stellate cells.
2020-01-01 | GSE108593 | GEO
Project description:Development of resistance causes failure of drugs targeting receptor tyrosine kinase (RTK) networks, and represents a critical challenge for precision medicine. Here we show that PHLDA1 down-regulation is critical to acquisition and maintenance of drug resistance in RTK-driven cancer. Using FGFR inhibition in endometrial cancer cells, we identify an Akt-driven compensatory mechanism underpinned by down-regulation of PHLDA1. We demonstrate broad clinical relevance of our findings, showing that PHLDA1 down-regulation also occurs in response to RTK-targeted therapy in breast and renal cancer patients, as well as following trastuzumab treatment in HER2+ breast cancer cells. Crucially, knockdown of PHLDA1 alone was sufficient to confer de novo resistance to RTK inhibitors, and induction of PHLDA1 expression re-sensitised drug resistant cancer cells to targeted therapies, identifying PHLDA1 as a biomarker for drug response and highlighting the potential of PHLDA1 reactivation as a means of circumventing drug resistance.
2018-03-05 | PXD008859 | Pride