Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells.
Cell Stem Cell
; 28(9): 1657-1670.e10, 2021 09 02.
Article
em En
| MEDLINE
| ID: mdl-33961804
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.
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Prader-Willi
/
Células-Tronco Pluripotentes Induzidas
Idioma:
En
Revista:
Cell Stem Cell
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos