5b35f1d9-1bf2-4f10-8855-5a6af7c5ddd1 - samples
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PROVIDER: EGAD00001006624 | EGA |
REPOSITORIES: EGA
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Project description:Neuroblastoma is a pediatric tumor of the developing sympathetic nervous system. However, the cellular origin of neuroblastoma remains to be defined. Here, we study single-cell transcriptomes of neuroblastomas and normal human developing adrenal glands at various stages of embryonic and fetal development. We define normal differentiation trajectories during adrenal medullary development and identify the cellular origin of neuroblastoma. Importantly, adrenergic and mesenchymal neuroblastomas with varying clinical phenotypes match different temporal states along normal differentiation trajectories, with the degree of differentiation corresponding to clinical prognosis.
| EGAS00001004388 | EGA
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: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
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.
2013-06-06 | GSE40398 | GEO
Project description:During embryonic development, nerve-associated Schwann cell precursors (SCPs) give rise to chromaffin cells of the adrenal gland via the “bridge” transient stage, according to recent functional experiments and single cell data from humans and mice. However, currently existing data do not resolve the finest heterogeneity of developing chromaffin populations. Here we took advantage of deep SmartSeq2 transcriptomic sequencing to expand our collection of individual cells from developing murine sympatho-adrenal anlage and uncover the microheterogeneity of embryonic chromaffin cells and corresponding developmental paths. After improving our atlas of sympatho-adrenal development and performing experimental validations, we discovered that SCPs in the local nerve show high degree of microheterogeneity corresponding to early biases towards either Schwann or chromaffin terminal fates. Furthermore, we found that a post-“bridge” population of developing chromaffin cells gives rise to persisting immature chromaffin cells and the two terminal populations (adrenergic and noradrenergic) via diverging differentiation paths. Taken together, we provide a thorough identification of novel markers of adrenergic and noradrenergic populations in developing adrenal glands and report novel differentiation micro-paths leading to them.
2022-05-27 | GSE204700 | GEO
Project description:The human adrenal glands are highly dynamic endocrine organs that are involved in the secretion of various hormones such as steroids and catecholamines. Here we present a single-nuclei and spatial transcriptomic analysis of healthy adult human adrenal glands to provide a complete adrenal gland atlas. With this, we show how such an atlas can be taken advantage when studying adrenocortical diseases, such as adrenocortical adenomas (ACA). Using nornal adrenal as reference, we showed a high intra-tumoural heterogeneity in the single-nuclei transcriptome of ACA, revealing the presence of specific cell populations associated with cortisol secretion and genetic background.
2023-01-01 | E-MTAB-12129 | biostudies-arrayexpress
Project description:Analysis of ACTH-regulation on adrenocortical cells at gene expression level. The hypothesis tested in the present study was that ACTH increases chronic cell growth and steroidogenesis in adrenal glands by changing the gene expression profile. Results provide important information on the changes of gene expression of adrenocortical cells after chronic ACTH treatment. Total RNA obtained from primary cultured fetal adrenal cells subjected to 48 hours in vitro treatment of ACTH compared to untreated control cell.
2010-07-08 | E-GEOD-20675 | biostudies-arrayexpress
Project description:To clarify the effects of endotoxin-induced intrauterine inflammation on the HPA axis of periviable sheep fetuses, fetal sheep (0.63 term) were divided into two groups: (1) the endotoxin group, in which the endotoxin was injected into the amniotic fluid and (2) the control group, in which the saline solution was injected instead. Gene expression levels in the fetal adrenal glands of each group were analyzed by RNA-seq.
2023-07-28 | GSE230267 | GEO
Project description:Neuroblastoma is a childhood cancer believed to result from dysfunctional development. Its origin during embryogenesis remains poorly understood. The lack of appropriate models has hindered in-depth mapping of early tumor-driving events. Here, we identify a novel tumor suppressor gene associating with worse outcome in MOXD1-deprived high-risk patients, by applying bulk and single cell RNA sequencing data of neuroblastoma and human fetal adrenal glands. Trunk neural crest-specific MOXD1 discriminates cell populations during normal and tumor development, with implications for deciphering neuroblastoma cell origin. We created an embryonic conditional knockout model and show that cell type-specific loss of MOXD1 leads to disrupted organ homeostasis and failed adrenal gland formation, home for neuroblastoma. We show that MOXD1 is a tumor suppressor gene in zebrafish, chick, and mice in vivo models.
2023-09-06 | GSE242157 | GEO
Project description:Gonadectomy (GDX) induces sex steroid-producing adrenocortical tumors in certain mouse strains and in the domestic ferret. Complementary approaches, including DNA methylation mapping and microarray expression profiling, were used to identify novel genetic and epigenetic markers of GDX-induced adrenocortical neoplasia in female DBA/2J mice. Markers were validated by quantitative RT-PCR, laser capture microdissection, in situ hybridization, and immunohistochemistry. Two genes with hypomethylated promoters, Igfbp6 and Foxs1, were upregulated in post-GDX adrenocortical neoplasms. The neoplastic cells also exhibited hypomethylation of the fetal adrenal enhancer of Sf1, an epigenetic signature that typifies descendants of fetal adrenal rather than gonadal cells. Expression profiling demonstrated upregulation of gonadal-like genes, including Spinlw1, Insl3, and Foxl2, in GDX-induced adrenocortical tumors of the mouse. One of these markers, FOXL2, was detected in adrenocortical tumor specimens from gonadectomized ferrets. These new markers may prove useful for studies of steroidogenic cell development and for diagnostic testing. Total RNA extracted from whole adrenal glands of gonadectomized and non-gonadectomized mice.
2014-07-31 | E-GEOD-54393 | biostudies-arrayexpress