Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196700 | GEO | 2023/06/12
REPOSITORIES: GEO
Similar Datasets
Project description:Evaluation of whole blood DNA methylome in 94 samples obtained from 47 patients with different glucocorticoid states, including Cushing’s syndrome, eucortisolism and adrenal insufficiency, in order to identify a molecular signature reflecting glucocorticoid action.
2022-01-19 | E-MTAB-10092 | biostudies-arrayexpress
Project description:Mutations in the catalytic subunit of protein kinase A (PKAc) drive the stress hormone disorder adrenal Cushing’s syndrome. We define mechanisms of action for the PKAcL205R and W196R variants. Proximity proteomic techniques demonstrate that both Cushing’s mutants are excluded from A kinase anchoring protein (AKAP) signaling islands, whereas live-cell photoactivation microscopy reveals that these kinase mutants indiscriminately diffuse throughout the cell. Only cAMP analog drugs that displace native PKAc from AKAPs enhance cortisol release. Rescue experiments that incorporate PKAc mutants into AKAP complexes abolish cortisol overproduction, indicating that kinase anchoring restores normal endocrine function. Analyses of adrenal-specific PKAc-W196R knock-in mice and Cushing’s syndrome patient tissue reveal defective signaling mechanisms of the disease. Surprisingly each Cushing’s mutant engages a different mitogenic signaling pathway, with upregulation of YAP/TAZ by PKAc-L205R and ERK kinase activation by PKAc-W196R. Thus, aberrant spatiotemporal regulation of each Cushing’s variant promotes the transmission of distinct downstream pathogenic signals.
2022-07-12 | PXD030888 | Pride
Project description:Gene expression was studied using PancChip5.0 in 15 tissues. Most tissues were from the adult mouse, except for fetal pancreas (e18.5) and placenta. Adult tissues studied were: adrenal gland, pancreas, brain, heart, kidney, liver, lung, ovary, parotid gland, pituitary gland, small intestine, stomach and testis. All were studied in duplicate except for the pituitary, the liver, and the stomach. All samples were pooled samples. Tissues were taken from 3 males and 3 females, with the exception of the gonadal tissues, and the fetal tissues were sex was not determined.
2014-12-04 | E-MTAB-3151 | biostudies-arrayexpress
Project description:Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues
| PRJNA806920 | ENA
Project description:Human fetal adrenal glands are huge endocrine organ, produce prodigious quantities of dehydroepiandrosterone and its sulfate (DHEA/DHEAS), which is the most prominent precursor for steroid hormones, adrenal gonads dysfunction leads to states of virilization or effemination. However, for a long time the function of fetal adrenal in initial sex differentiation is unclear. Herein, we draw out a single-cell transcriptional landscape of human fetal adrenals and gonad from 6 to 14 gestational weeks (GW). We found that the adrenal glands begin to express CYP17A1 steroid-related enzyme much early than testis, subsequent testis steroid express pattern support de novo or halfway testosterone synthesis. Excepted steroidogenic cell, notably, the immune cells or neurocyte shows steroid metabolism or regulation ability, such as CD5L+ macrophage interacted with steroidogenic cell and SRD5A1+ AKR1C2+ chromaffin cells synthesis active testosterone DHT through backdoor pathway. Sex different were found at adrenal glands and gonad development: there is a small HSD3B2 peak occurs only in female adrenal glands around 10-12 GW within the time window of sex differentiation. SST expression levels or SST+ cells quantity in adrenal glands and gonads are different in two gender. Our research indicates that a sex different in spatial and temporal disparities steroidogenic regulatory networks in adrenal glands and gonads, facilitating further exploration of development and physiology of human adrenal glands.
2022-08-08 | GSE167860 | GEO
Project description:Gene expression profiles of somatic cells of fetal and adult testis. To identify genes developmentally regulated in the somatic cells of the testis, serial analysis of gene expression (SAGE) has been used to generate gene expression profiles from these cells in the fetal and adult mouse. To avoid germ cell transcripts, a fetal SAGE library was generated from germ cell-free fetal Wv/Wv mice, and an adult SAGE library was generated from adult testes depleted of germ cells with busulfan. The combined SAGE libraries contained 147570 tags identifying 12976 unique transcripts. Of these transcripts, 3607 were present in only the fetal library and 3941 were present in only the adult library. Most of the abundant differentially expressed tags in the adult testis library were from characterized genes, whereas 3' rapid amplification of complementary ends was required to identify most differentially expressed tags in the fetal library. These fetal tags were mostly associated with uncharacterized UniGene clusters. These data provide a comprehensive and quantitative analysis of gene expression in the somatic cells of the fetal and adult testis (including unknown transcripts) and identify genes differentially expressed in these cells during testis development. These differentially regulated genes are likely to provide insight into mechanisms regulating testis function both during development and in the adult animal. Keywords: other
2003-05-06 | GSE366 | GEO
Project description:Adrenal Cushing’s syndrome is a disease of cortisol hypersecretion often caused by mutations in protein kinase A catalytic subunit (PKAc). Using a personalized medicine screening platform, we discovered a new Cushing’s driver mutation, PKAc-W196G, in ~20% of patient samples analyzed. Proximity proteomics and photokinetic imaging reveal that PKAcW196G is distinct from other Cushing’s variants. This mutant surprisingly retains association with type I regulatory subunits (RI) and their corresponding A kinase anchoring proteins (AKAPs). Molecular dynamics simulations predict that substitution of glycine for tryptophan 196 creates a 653 Å3 cleft between the catalytic core of PKAcW196G and type II regulatory subunits (RII), but only a 395 Å3 cleft with RI. Endocrine measurements show that overexpression of RIα or redistribution of PKAcW196G via AKAP recruitment counteracts stress hormone overproduction. We conclude that a W196G mutation in the kinase catalytic core skews R subunit selectivity and biases AKAP association to drive Cushing’s syndrome.
2024-02-10 | PXD045556 | Pride
Project description:We performed WES for 8 cases with corticotropin-independent Cushing’s syndrome, in whom paired tumor and normal DNA was obtained from fresh frozen adenomas and either normal adrenal tissues or peripheral blood, respectively.
| EGAS00001000661 | EGA
Project description:Gene expression profiles of somatic cells of fetal and adult testis. To identify genes developmentally regulated in the somatic cells of the testis, serial analysis of gene expression (SAGE) has been used to generate gene expression profiles from these cells in the fetal and adult mouse. To avoid germ cell transcripts, a fetal SAGE library was generated from germ cell-free fetal Wv/Wv mice, and an adult SAGE library was generated from adult testes depleted of germ cells with busulfan. The combined SAGE libraries contained 147570 tags identifying 12976 unique transcripts. Of these transcripts, 3607 were present in only the fetal library and 3941 were present in only the adult library. Most of the abundant differentially expressed tags in the adult testis library were from characterized genes, whereas 3' rapid amplification of complementary ends was required to identify most differentially expressed tags in the fetal library. These fetal tags were mostly associated with uncharacterized UniGene clusters. These data provide a comprehensive and quantitative analysis of gene expression in the somatic cells of the fetal and adult testis (including unknown transcripts) and identify genes differentially expressed in these cells during testis development. These differentially regulated genes are likely to provide insight into mechanisms regulating testis function both during development and in the adult animal. Keywords: other
2003-05-06 | E-GEOD-366 | biostudies-arrayexpress
Project description:Transcription factor GATA6 is expressed in the fetal and adult adrenal cortex and has been implicated in steroidogenesis. To characterize the role of GATA6 in adrenocortical development and function, we generated mice in which Gata6 was conditionally deleted using Cre-LoxP recombination with Sf1-cre. The adrenal glands of adult Gata6 conditional knockout (cKO) mice were small and had a thin cortex with thickened capsule. Cytomegalic changes were evident in the adrenal glands of fetal and adult cKO mice, and chromaffin cells were ectopically located at the periphery of the glands. The secretion of corticosterone in response to exogenous ACTH was blunted in cKO mice. Cells expressing gonadal-like markers, including Gata4, Amhr2, and Tcf21, accumulated in the adrenal capsule and subcapsule of cKO mice, suggesting aberrant adrenocortical progenitor/stem cell differentiation. Gonadectomy triggered the overexpression of sex steroidogenic differentiation markers, such as Lhcgr and Cyp17, in the adrenal glands of male and female cKO mice. Nulliparous female and orchiectomized male cKO mice lacked an adrenal X-zone. Microarray hybridization identified Pik3c2g as a novel X-zone marker that is downregulated in the adrenal glands of nulliparous female Gata6 cKO mice. Our findings offer genetic proof of the longstanding hypothesis that GATA6 regulates the differentiation of steroidogenic progenitors into corticoid-producing cells. 3 replicates from both conditional knockout of Gata6 in the adrenal gland and control adrenal glands from non-knockout mice were compared
2013-06-06 | E-GEOD-40398 | biostudies-arrayexpress