{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huang WK"],"funding":["NIMH","NIAID NIH HHS","NIMH NIH HHS","Foundation for Prader-Willi Research","NINDS NIH HHS","National Institutes of Health","NINDS"],"pagination":["1657-1670.e10"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8419002"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["28(9)"],"pubmed_abstract":["Human brain organoids represent remarkable platforms for recapitulating features of human brain development and diseases. Existing organoid models do not resolve fine brain subregions, such as different nuclei in the hypothalamus. We report the generation of arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) to model the development of the human hypothalamic arcuate nucleus. Single-cell RNA sequencing of ARCOs revealed significant molecular heterogeneity underlying different arcuate cell types, and machine learning-aided analysis based on the neonatal human hypothalamus single-nucleus transcriptome further showed a human arcuate nucleus molecular signature. We also explored ARCOs generated from Prader-Willi syndrome (PWS) patient iPSCs. These organoids exhibit aberrant differentiation and transcriptomic dysregulation similar to postnatal hypothalamus of PWS patients, indicative of cellular differentiation deficits and exacerbated inflammatory responses. Thus, patient iPSC-derived ARCOs represent a promising experimental model for investigating nucleus-specific features and disease-relevant mechanisms during early human arcuate development."],"journal":["Cell stem cell"],"pubmed_title":["Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells."],"pmcid":["PMC8419002"],"funding_grant_id":["R35 NS097370","R35 NS116843","RF1MH123979","R35NS116843","R35NS097370","U19 AI131130","RF1 MH123979"],"pubmed_authors":["Zhang F","Chen L","Song H","Nguyen PTT","Pather SR","Lu L","Fernandes A","Zhang Z","Huang WK","Fang W","Wong SZH","Ming GL","Zhang DY","Su Y"],"additional_accession":[]},"is_claimable":false,"name":"Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.","description":"Human brain organoids represent remarkable platforms for recapitulating features of human brain development and diseases. Existing organoid models do not resolve fine brain subregions, such as different nuclei in the hypothalamus. We report the generation of arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) to model the development of the human hypothalamic arcuate nucleus. Single-cell RNA sequencing of ARCOs revealed significant molecular heterogeneity underlying different arcuate cell types, and machine learning-aided analysis based on the neonatal human hypothalamus single-nucleus transcriptome further showed a human arcuate nucleus molecular signature. We also explored ARCOs generated from Prader-Willi syndrome (PWS) patient iPSCs. These organoids exhibit aberrant differentiation and transcriptomic dysregulation similar to postnatal hypothalamus of PWS patients, indicative of cellular differentiation deficits and exacerbated inflammatory responses. Thus, patient iPSC-derived ARCOs represent a promising experimental model for investigating nucleus-specific features and disease-relevant mechanisms during early human arcuate development.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Sep","modification":"2026-05-31T16:04:59.264Z","creation":"2025-02-19T01:27:46.759Z"},"accession":"S-EPMC8419002","cross_references":{"pubmed":["33961804"],"doi":["10.1016/j.stem.2021.04.006"]}}