{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE291nnn/GSE291218/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE291218"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Functional reconstitution of adrenocortical transdifferentiation from human pluripotent stem cells","description":"Proper prenatal adrenal cortex development is essential to prevent life-threatening adrenal insufficiency. This process relies on self-renewing progenitor cells within a capsule (Cap)-derived niche of the definitive zone (DZ) and trans-differentiation into cortisol-producing transitional and androgen-producing fetal zones. However, species-specific limitations in rodent models hinder mechanistic insights. To address this, we developed a human iPSC-derived organoid system that mimics prenatal adrenal development. Our advanced platform efficiently generates DZ-like cells (DZLCs) and Cap-like cells (CapLCs), revealing that DZLCs arise from adrenal primordium-like cells (APLCs) and are sustained via CapLC-derived RSPO3/WNT signaling. These DZLCs trans-differentiate into transitional and fetal zone-like cells (FZLCs) through ACTH and RSPO3 signaling. Notably, NR0B1 loss impairs DZLC specification while driving direct APLC-to-FZLC conversion, recapitulating NR0B1 mutation-associated X-linked adrenal hypoplasia congenita. Notably, DZLCs encapsulated with CapLCs form ACTH-responsive, cortisol-producing cortical tissue in vivo, demonstrating therapeutic potential. These organoid models offer a powerful platform for adrenal research and lay the groundwork for cell-based therapies for adrenal insufficiency.","dates":{"publication":"2026/05/05"},"accession":"GSE291218","cross_references":{"GSM":["GSM8831089","GSM8831100","GSM8831101","GSM8831098","GSM8831099","GSM8831104","GSM8831105","GSM8831102","GSM8831103","GSM8831092","GSM8831093","GSM8831090","GSM8831091","GSM8831096","GSM8831097","GSM8831094","GSM8831095"],"GPL":["30173"],"GSE":["291218"],"taxon":["Homo sapiens"],"PMID":["[41795428]"]}}