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

Autor:	Sarrafha L; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Neavin DR; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia., Parfitt GM; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Kruglikov IA; New York Stem Cell Foundation, New York, NY 10019, USA., Whitney K; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Department of Pathology, Molecular, and Cell-Based Medicine, Mount Sinai, New York, NY 10029, USA., Reyes R; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Coccia E; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Kareva T; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Goldman C; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Tipon R; New York Stem Cell Foundation, New York, NY 10019, USA., Croft G; New York Stem Cell Foundation, New York, NY 10019, USA., Crary JF; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Department of Pathology, Molecular, and Cell-Based Medicine, Mount Sinai, New York, NY 10029, USA.; Windreich Department of Artificial Intelligence and Human Health, Mount Sinai, New York, NY 10029, USA., Powell JE; Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.; UNSW Cellular Genomics Futures Institute, University of New South Wales, Kensington, Sydney, NSW 2052, Australia., Blanchard J; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA., Ahfeldt T; Nash Family Department of Neuroscience, Mount Sinai, New York, NY 10029, USA.; Department of Neurology, Mount Sinai, New York, NY 10029, USA.; Department of Cell, Developmental and Regenerative Biology, Mount Sinai, New York, NY 10029, USA.; Ronald M. Loeb Center for Alzheimer's Disease, Mount Sinai, New York, NY 10029, USA.; Friedman Brain Institute, Mount Sinai, New York, NY 10029, USA.; Black Family Stem Cell Institute, Mount Sinai, New York, NY 10029, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2023 Aug 02; Vol. 26 (9), pp. 107525. Date of Electronic Publication: 2023 Aug 02 (Print Publication: 2023).
DOI:	10.1016/j.isci.2023.107525
Abstrakt:	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. Competing Interests: The authors declare no competing interests. (© 2023 The Authors.)
Databáze:	MEDLINE
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