Project description:The regulation of pituitary function via the hypothalamus and via intra-pituitary connections represents a complex system. Though hormones secreted from the pituitary glands have been well studied, overall information of proteins expressed in the pituitary glands is very limited. Protein expression profiling of normal pituitary tissue may lead to discovery of novel proteins playing an important role in the physiology of pituitary glands and can lead to better understanding of pituitary gland diseases. We aimed to carry out systematic proteomic profiling of adenohypophysis from human pituitary glands using high-resolution Fourier transform mass spectrometer. A total of 2,175 proteins were identified in this study of which, 105 proteins were identified for the first time as compared to high throughput proteomic-based studies from human pituitary glands. The comprehensive list of proteins identified in this study will facilitate the better understanding the role of this important gland in health and disease.
Project description:This series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue; Data Transformation; Using Affymetrix Microarray Suite 5.0 global scaling was applied to the quantification data to adjust the average recorded to a target intensity of 100. Data were then exported into the bioinformatics software GeneSpring 6.0 (Silicon Genetics, Redwood City, CA) for further analysis. Data normalization was performed to scale the data so that the average intensity value on each array was 1 by dividing each expression value by the median of the expression levels on each chip. The individual gene expression levels for each of the 4 pituitary adenoma subtype arrays was divided by the expression level in the normal pituitary array. Thus, the data are presented as relative to the expression in normal pituitary tissue. Filtering was then performed to identify genes over-expressed or under-expressed at least 2.0 fold in tumours compared to normal pituitary. TABLE 1:; The genes / ESTs differentially overexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given. TABLE 2:; The genes / ESTs differentially underexpressed >= 2-fold in at least one pituitary adenoma subtype compared to normal pituitary. Negative values represent underexpression. Where genes are represented by more than one probe set, individual probe data sets are given.
Project description:Analysis the different gene expression of prolactinomas and normal pituitary tissues. Prolactinoma is a benign pituitary tumor that produces excessive prolactin resulting in hyperprolactinemia and another disease.Tissues were microdissected and removed using the surgical microscope, rinsed in sterile saline, snap-frozen in liquid nitrogen, and stored (-80 ℃) until analysis. Results provide insight into understanding the difference of gene expression in prolacinomas.
Project description:The anterior pituitary gland plays central roles in body growth, reproduction, metabolism and the stress response. In this study, we performed single-cell RNA-sequencing (scRNA-seq) of 4,113 individual cells from human fetal pituitaries. We characterized divergent developmental trajectories with distinct transitional intermediate states in five hormone-producing cell lineages. Furthermore, we characterized the cellular heterogeneity of pituitary stem cells, identifying a hybrid epithelial/mesenchymal state and an early-to-late state transition. These analyses define a single-cell resolution roadmap for human pituitary development.
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
Project description:Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function and cortisol production. Although recently determined to be monoclonal, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. Surgical resection is the treatment of choice for most symptomatic pituitary adenomas. The goal of surgery is the complete removal of the tumor and the success of surgery is strongly affected by the presence of local invasion. However, complete tumor removal is unlikely when there is extensive local invasion. Identifying genes that control the invasiveness and recurrence of this class of tumors will provide therapeutic targets for this class of tumors. We will determine the expression pattern of genes in recurrent and invasive and pituitary adenomas and compare those to non-invasive and non-recurrent tumors. We hypothesize that the differential expression and activation of a number of genes affect pituitary adenoma recurrence and invasiveness. Rationale: Preliminary result showed a differential expression of novel PKC isozymes in non-invasive and invasive pituitary adenomas. PMA, an activator of both novel and classical PKC isozymes increased the expression of gelatinase A (MMP-2) mRNA in human pituitary adenoma cell line. This result raises a fundamental question as to the functional role of novel PKC isozymes and proteases in the invasive phenotype of pituitary adenomas. The primary component of this Specific Aim is to determine whether specific genes are differentially expressed in recurrent or invasive adenomas when compared with control non-invasive tumors. Tissue specimens from non-invasive and invasive (dural invasion based microscopic examination) and recurrent vs non-recurrent tumors will be used for microarray analysis. Frozen pituitaryspecimens will be collected and total RNA extracted with TriZol reagent. We will provide total RNA (10 ug) from non-invasive, invasive, reoccurred and non-occurrent pituitary adenomas.
Project description:Single nucleus pituitary transcriptomic and epigenetic landscape reveals human stem cell heterogeneity with diverse regulatory mechanisms
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.
Project description:Pituitary adenomas are benign tumors originating from the endocrine cells of the pituitary gland, but some pathological subtypes are highly invasive, known as invasive pituitary adenomas. Invasive pituitary adenomas are relatively rare, progress rapidly, easily invade surrounding tissues, have a high risk of recurrence, and have poor response to standard treatments. This study collected tumor specimens from 17 patients with non-invasive pituitary adenomas (FSH type) and 15 patients with invasive pituitary adenomas (ACTH-silent type), and performed transcriptome sequencing, aiming to explore the genetic differences between invasive and non-invasive pituitary adenomas.