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Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [bulk RNA-seq]

ABSTRACT: Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [bulk RNA-seq]

PROVIDER: PRJNA833063 | ENA |

REPOSITORIES: ENA

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Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [bulk RNA-seq]

Project description:The adrenal cortex produces vital steroid hormones that maintain homeostasis. While steroid hormones produced from the fetal zone adrenal cortex are essential for both fetal development and maintenance of pregnancy, the molecular mechanisms leading to human adrenal cortex development and steroid synthesis remain poorly understood due to the paucity of model systems. Through progressive generation of fetal zone adrenal cortex-like cells (FZLCs) from human induced pluripotent stem cells through posterior intermediate mesoderm-like, adrenogenic coelomic epithelium and adrenal primordium-like states, we provide the first in vitro reconstitution of human adrenocortical fetal specification. Generation of FZLCs faithfully recapitulates human embryonic adrenal cortex specification as evidenced by histomorphological and ultrastructural analysis, transcriptional profiles and delta-5 steroid biosynthesis and occurs in an adrenocorticotropic hormone (ACTH)-independent manner, consistent with clinical observations. Furthermore, we demonstrate that FZLC generation is promoted by SHH and inhibited by NOTCH, ACTIVIN and WNT signaling and that steroid synthesis is amplified by ACTH/PKA signaling and blocked by pharmacologic inhibitors of delta 5 steroid synthesis enzymes. Finally, NR5A1 appear to self-stabilize its promoter activity and promote FZLC survival and steroidogenesis. Together, these findings provide a framework for understanding and reconstituting human adrenocortical development in vitro and pave the way for future cell-based therapies of adrenal insufficiency.

2022-10-16 | GSE201792 | GEO

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells

Project description:Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells

| PRJNA833058 | ENA

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scRNA-seq]

2022-10-16 | GSE201794 | GEO

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scATAC-seq]

2022-10-16 | GSE201793 | GEO

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scRNA-seq]

Project description:Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scRNA-seq]

| PRJNA833060 | ENA

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scATAC-seq]

Project description:Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells [scATAC-seq]

| PRJNA833062 | ENA

Comprehensive analysis of adrenocortical steroidogenesis in human and mouse

Project description:We analyze gene regulatory mechanisms involved in adrenocortical steroidogenesis using assays to measure RNA expression, synthesis, decay, processing, translation and miRNA expression.

2021-08-29 | GSE100391 | GEO

Reconstitution of human adrenocortical specification and steroidogenesis using induced pluripotent stem cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-10-16 | GSE201795 | GEO

Comprehensive analysis of adrenocortical steroidogenesis in human and mouse

Project description:Comprehensive analysis of adrenocortical steroidogenesis in human and mouse

| PRJNA391696 | ENA

Compound-induced NR5A1 exon-skipping and circular-RNA expression show impaired steroidogenesis in adrenocortical cancer cells

Project description:Despite the intensive search for an effective drug to treat steroid-producing adrenocortical carcinomas, there are few therapeutic options. We sought whether splicing modifying compounds are effective on this devastating disease. Here, we show that a chemical compound in clinical trial, CX-4945, suppressed the expression of NR5A1 through aberrant multiple exon skipping leading to suppressed steroidogenesis and induced dysfunctional autophagy and progression to ER-stress-related apoptosis. A circular RNA of NR5A1 exons with an IRE1α-cleavage site on the ligated ends (circAd4BP HAC1-type ex1-6 RNA) is expressed in normal adrenal cortex but not in H295R adrenocortical cancer cells, and CX-4945 induced a different circular RNA of NR5A1 exons (circAd4BP ex2-4 RNA). This potential pharmacological control of abnormal steroidogenesis through NR5A1 aberrant splicing and interplay with its circAd4BP makes CX-4945 a strong candidate novel drug for the treatment of adrenocortical carcinomas.

2018-09-25 | GSE120325 | GEO

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