Integration of RNA-Seq and ATAC-Seq Identifies Key Genes and chromatin accessibility changes in Growth hormone-secreting pituitary adenoma
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ABSTRACT:
PROVIDER: PRJNA755271 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15466832_1.fastq.gz | Fastqsanger.gz | |||
| SRR15466832_2.fastq.gz | Fastqsanger.gz | |||
| SRR15466834_1.fastq.gz | Fastqsanger.gz | |||
| SRR15466834_2.fastq.gz | Fastqsanger.gz | |||
| SRR15466835_1.fastq.gz | Fastqsanger.gz |
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Project description:Data from 12 fresh-frozen somatotropinomas and their corresponding blood samples. Details are given in Valimaki et al. Whole-genome sequencing of Growth Hormone (GH) -secreting Pituitary Adenoma. Provisionally accepted, 2015.
| EGAS00001001293 | EGA
Project description:We profiled the somatic landscape of 21 growth hormone (GH) -secreting pituitary adenomas using somatic copy-number alteration (SCNA), whole-genome sequencing (WGS), bisulfate sequencing, and transcriptome approaches. See details in Valimaki et al. Genetic and epigenetic characterization of growth hormone (GH) - secreting pituitary tumors. Manuscript in preparation, 2019.
| EGAS00001003488 | EGA
Project description:Background: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, leading to increased morbidity and mortality. Though treatments for GHPA have greatly improved, lack of deep knowledge on the precise molecular mechanisms involved in GHPA hinders the development of therapeutic approaches. Few studies have attempted to reveal the genome-wide landscape of GHPA. As chromatin structure change exerts significant influence on gene transcription, herein, we investigated the landscape of chromatin accessibility. Methods: Both assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were applied to identify the differential expression genes (DEGs) and uncover chromatin accessibility changes and the potentially associated transcription factor (TFs) in somatotropinoma tissues. Results: 64 DEGs were obtained, including 10 DEGs were elevated in the tumors and 54 DEGs were negligibly expressed in adenomas. A total of 3916 increased and 2895 decreased chromatin-accessible regions were identified nearby these DEGs. The majority of DEGs associated with closed chromatin regions were significantly down-regulated in our study, while the most of DEGs near open chromatin were not expectantly up-regulated. Additionally, the newly opened and closed chromatin regions were highly enriched for GRE and CTCF transcription factor binding sites, which were potentially relevant to the regulation of chromatin accessibility and genes expression in GHPA. Conclusion: Collectively, our results reveal the landscape of chromatin accessibility and unique enhancer in GHPA, which may, at least in part, contribute to tumorigenesis and provide a new field of drug development.
2021-08-18 | GSE182180 | GEO
Project description:Corticotropin (ACTH)-secreting pituitary adenomas give rise to a severe endocrinological disorder, i.e., Cushing’s disease, with multifaceted clinical presentation and treatment outcomes. Experimental studies suggested that disease variability is inherent to the pituitary tumor, thus pointing to the need for further studies into tumor biology. Aim of the present study was to evaluate transcriptome expression pattern in a large series of ACTH-secreting pituitary adenoma specimens, in order to identify molecular signatures of these tumors. Gene expression profiling of formalin-fixed paraffin-embedded specimens from 40 human ACTH-secreting pituitary adenomas revealed significant expression of genes involved in protein biosynthesis and ribosomal function, in keeping with neuroendocrine cell profile. Unsupervised cluster analysis identified three distinct gene profile clusters and several genes were uniquely overexpressed in a given cluster, accounting for different molecular signatures. Of note, gene expression profiles were associated with clinical features such as age and size of the tumor. Altogether, our study shows that corticotrope tumors are characterized by neuroendocrine gene expression profile and present subgroup-specific molecular features.
2018-06-18 | GSE93825 | GEO
Project description:This study investigated differential gene expression between granulation patterns in growth hormone (GH)-secreting pituitary tumors, aiming to elucidate novel transcriptomes that explain clinical variances in patients with acromegaly. Transcriptome analysis was conducted on 6 normal pituitary tissues and 15 GH-secreting pituitary tumors, including 9 densely granulated somatotroph tumors (DGSTs) and 6 sparsely granulated somatotroph tumors (SGSTs). We identified 3111 differentially expressed genes (DEGs) in tumors compared to normal pituitaries, with 1117 DEGs unique to a specific granulation within tumors. SGST showed enrichment of neuronal development and acute inflammatory response pathways, along with a significant enhancement of JAK–STAT, phosphatidylinositol 3-kinase, and MAPK signaling. The results suggest that granulation-specific gene expression may underpin diverse clinical presentations in acromegaly, highlighting the potential for further investigation into these transcriptomic variations and their roles in disease pathology, particularly the involvement of genes linked to neuronal development, inflammatory response, and JAK–STAT signaling in SGST.
2024-04-28 | GSE264621 | GEO
Project description:Gut bacteria induce IgA expression in pituitary hormone-secreting cells during aging
| PRJNA999204 | ENA
Project description:The differential gene screening for invasive pituitary adenoma and non-invasive pituitary adenoma
| PRJNA1081873 | ENA
Project description:Background: Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression. Aim: Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma. Materials and Methods: 149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data. Results: Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02). Conclusions: Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
2019-05-21 | GSE131483 | GEO
Project description:Objective Circulating plasma miRNAs have been increasingly studied in the field of pituitary neuroendocrine tumor (PitNET) research. Our aim was to discover circulating plasma miRNAs species associated with growth hormone (GH) secreting PitNETs and assess how the plasma levels of discovered miRNA candidates are impacted by SSA therapy and whether there is a difference in their levels between GH secreting PitNETs and other PitNET types. Methods miRNA candidates were discovered using the whole miRNA sequencing approach and differential expression analysis. Selected miRNAs were then analyzed using real-time polymerase chain reaction (qPCR). Results Whole miRNA sequencing discovered a total of 19 differentially expressed miRNAs (DEMs) in GH secreting PitNET patients' plasma 24 hours after surgery and 19 DEMs between GH secreting PitNET patients’ plasma and non-functioning (NF) PitNET patients’ plasma. Seven miRNAs were selected for further testing of which miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p showed a significant downregulation in plasma after 1 month of SSA treatment. miR-181a-5p and mir-625-5p were also found to be significantly downregulated in plasma of GH secreting PitNET patients vs. NF PitNET patients. Conclusions Our study suggests that expression of plasma miRNAs miR-625-5p, miR-503-5p miR-181a-2-3p and miR-130b-3p in GH secreting PitNETs is affected by SSA treatment. Additionally, miR-625-5p and miR-181a-5p can distinguish GH secreting PitNETs from other PitNET types warranting further research on these miRNAs for treatment efficacy.
2022-02-16 | GSE196647 | GEO
Project description:Inter-organ communication is a major hallmark of health and is often orchestrated by hormones released by the anterior pituitary gland. Pituitary gonadotropes secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to regulate gonadal function and control fertility. Whether FSH and LH also act on organs other than the gonads is debated. Here, we found that gonadotrope depletion in adult female mice triggers profound hypogonadism, obesity, glucose intolerance, fatty liver, and bone loss. The absence of sex steroids precipitates these phenotypes, with the notable exception of fatty liver, which results from ovary-independent actions of FSH. We uncover paracrine FSH action on pituitary corticotropes as a novel mechanism to restrain the production of corticosterone and prevent hepatic steatosis. Our data demonstrate that functional communication of two distinct hormone-secreting cell populations in the pituitary regulates hepatic lipid metabolism.
2023-01-11 | GSE216096 | GEO