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Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity


The hypothalamus is a region of the brain that plays an important role in regulating body functions and behaviors. There is a growing interest in human pluripotent stem cells (hPSCs) for modeling diseases that affect the hypothalamus. Here, we established an hPSC-derived hypothalamus organoid differentiation protocol to model the cellular diversity of this brain region. Using an hPSC line with a tyrosine hydroxylase (TH)-TdTomato reporter for dopaminergic neurons (DNs) and other TH-expressing cells, we interrogated DN-specific pathways and functions in electrophysiologically active hypothalamus organoids. Single-cell RNA sequencing (scRNA-seq) revealed diverse neuronal and non-neuronal cell types in mature hypothalamus organoids. We identified several molecularly distinct hypothalamic DN subtypes that demonstrated different developmental maturities. Our in vitro 3D hypothalamus differentiation protocol can be used to study the development of this critical brain structure and can be applied to disease modeling to generate novel therapeutic approaches for disorders centered around the hypothalamus.

Type Journal
ISBN 2589-0042 (Electronic) 2589-0042 (Linking)
Authors Sarrafha, L.; Neavin, D. R.; Parfitt, G. M.; Kruglikov, I. A.; Whitney, K.; Reyes, R.; Coccia, E.; Kareva, T.; Goldman, C.; Tipon, R.; Croft, G.; Crary, J. F.; Powell, J. E.; Blanchard, J.; Ahfeldt, T.
Publisher Name iScience
Published Date 2023-09-15
Published Volume 26
Published Issue 9
Published Pages 107525
Status Published in-print
DOI 10.1016/j.isci.2023.107525
URL link to publisher's version