ESPEYB19 1. Pituitary and Neuroendocrinology Basic Science and Stem Cells (4 abstracts)
1.3. Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells
Huang WK , Wong SZH , Pather SR , Nguyen PTT , Zhang F , Zhang DY , Zhang Z , Lu L , Fang W , Chen L , Fernandes A , Su Y , Song H & Ming GL
Cell Stem Cell. 2021 Sep 2;28(9):1657-1670.e10. doi: 10.1016/j.stem.2021.04.006. PMID: 33961804.
Brief Summary: The authors established a novel protocol to generate hypothalamic arcuate organoids from human induced pluripotent stem cells, which could be utilized to investigate the arcuate nuclei development and the underlying mechanism of arcuate nucleus-related diseases.
Human three-dimensional (3D) brain organoids represent remarkable platforms for recapitulating features of human brain development and diseases. These 3D organoid models involve cell-cell and cell-matrix interactions and create better biomimetic tissue models than two-dimensional models. However, existing organoid models do not resolve fine brain subregions, such as different nuclei in the hypothalamus.
This study reported a protocol of generating arcuate organoids (ARCOs) from human induced pluripotent stem cells (iPSCs) to model the development of the human hypothalamic arcuate nucleus. These ARCOs exhibit similar cell type diversity and molecular signatures compared with the human arcuate nucleus (ARC) on single cell RNA sequencing analysis. The authors used this model to explore the development and function of ARCOs derived from Prader-Willi syndrome patient iPSCs (derived from fibroblasts). They found that patient iPSC-derived ARCOs exhibit aberrant differentiation and decreased leptin responses compared with control ARCOs. Furthermore, transcriptome analysis indicates that the patient-derived ARCOs show increased immune responses.
Thus, ARCOs derived from human iPSCs can be used to model early hypothalamic ARC developmental processes and investigate the mechanism of related brain diseases.
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ESPE Yearbook of Paediatric Endocrinology
ISSN 1662-4009 (Online)
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