A spatiotemporal regulatory network for steroidogenesis of human fetal adrenal glands and gonads
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ABSTRACT:
PROVIDER: PRJNA705264 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13799162.fastq.gz | Fastqsanger.gz | |||
| SRR13799163.fastq.gz | Fastqsanger.gz | |||
| SRR13799164.fastq.gz | Fastqsanger.gz | |||
| SRR13799165.fastq.gz | Fastqsanger.gz | |||
| SRR13799166.fastq.gz | Fastqsanger.gz |
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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.
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Project description:We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. Experiment Overall Design: In the current study, rat pups (with their dams) were exposed to hypoxia from birth and compared to pups from normoxic dams fed ad libitum. Adrenal glands were collected from normoxic and hypoxic pups at PD7and pooled (N=24/sample; 4 samples per treatment group) for total RNA extraction. Microarray analysis was performed, followed by verification with real-time PCR. Furthermore, the expression of selected genes involved in adrenal function was analyzed by real-time PCR, regardless of microarray results.
2008-06-14 | E-GEOD-6249 | biostudies-arrayexpress
Project description:We hypothesize that changes in adrenal gene expression mediate the increased plasma corticosterone and steroidogenesis in rat pups exposed to hypoxia from birth. Keywords: effects of hypoxia on adrenal steroidogenesis in the neonatal rat
2006-11-14 | GSE6249 | 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:Human fetal adrenal glands produce substantial amounts of dehydroepiandrosterone (DHEA), which is one of the most important precursors of sex hormones. However, the underlying biological mechanism remains largely unknown. Herein, we sequenced human fetal adrenal glands and gonads from 7 to 14 gestational weeks (GW) via 10× Genomics single-cell transcriptome techniques, reconstructed their location information by spatial transcriptomics. Relative to gonads, adrenal glands begin to synthesize steroids early. The coordination among steroidogenic cells and multiple non-steroidogenic cells promotes adrenal cortex construction and steroid synthesis. Notably, during the window of sexual differentiation (8-12 GW), key enzyme gene expression shifts to accelerate DHEA synthesis in males and cortisol synthesis in females. Our research highlights the robustness of the action of fetal adrenal glands on gonads to modify the process of sexual differentiation.
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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: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:We measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA. Keywords: other
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