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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 differ...

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Autores principales: Sarrafha, Lily, Neavin, Drew R., Parfitt, Gustavo M., Kruglikov, Ilya A., Whitney, Kristen, Reyes, Ricardo, Coccia, Elena, Kareva, Tatyana, Goldman, Camille, Tipon, Regine, Croft, Gist, Crary, John F., Powell, Joseph E., Blanchard, Joel, Ahfeldt, Tim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460991/
https://www.ncbi.nlm.nih.gov/pubmed/37646018
http://dx.doi.org/10.1016/j.isci.2023.107525
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author Sarrafha, Lily
Neavin, Drew R.
Parfitt, Gustavo M.
Kruglikov, Ilya A.
Whitney, Kristen
Reyes, Ricardo
Coccia, Elena
Kareva, Tatyana
Goldman, Camille
Tipon, Regine
Croft, Gist
Crary, John F.
Powell, Joseph E.
Blanchard, Joel
Ahfeldt, Tim
author_facet Sarrafha, Lily
Neavin, Drew R.
Parfitt, Gustavo M.
Kruglikov, Ilya A.
Whitney, Kristen
Reyes, Ricardo
Coccia, Elena
Kareva, Tatyana
Goldman, Camille
Tipon, Regine
Croft, Gist
Crary, John F.
Powell, Joseph E.
Blanchard, Joel
Ahfeldt, Tim
author_sort Sarrafha, Lily
collection PubMed
description 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.
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spelling pubmed-104609912023-08-29 Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity Sarrafha, Lily Neavin, Drew R. Parfitt, Gustavo M. Kruglikov, Ilya A. Whitney, Kristen Reyes, Ricardo Coccia, Elena Kareva, Tatyana Goldman, Camille Tipon, Regine Croft, Gist Crary, John F. Powell, Joseph E. Blanchard, Joel Ahfeldt, Tim iScience Article 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. Elsevier 2023-08-02 /pmc/articles/PMC10460991/ /pubmed/37646018 http://dx.doi.org/10.1016/j.isci.2023.107525 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Sarrafha, Lily
Neavin, Drew R.
Parfitt, Gustavo M.
Kruglikov, Ilya A.
Whitney, Kristen
Reyes, Ricardo
Coccia, Elena
Kareva, Tatyana
Goldman, Camille
Tipon, Regine
Croft, Gist
Crary, John F.
Powell, Joseph E.
Blanchard, Joel
Ahfeldt, Tim
Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title_full Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title_fullStr Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title_full_unstemmed Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title_short Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
title_sort novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10460991/
https://www.ncbi.nlm.nih.gov/pubmed/37646018
http://dx.doi.org/10.1016/j.isci.2023.107525
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