Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity.
Novel human pluripotent stem cell-derived hypothalamus organoids demonstrate cellular diversity.
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DOI：
10.1016/j.isci.2023.107525
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发表时间：
2023-09-15
期刊：
影响因子：
5.8
通讯作者：
Ahfeldt, Tim
中科院分区：
文献类型：
--
作者：
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
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. We established a novel protocol for generating hypothalamus organoids in vitro Mature hypothalamus organoids consisted of 11 broad cell types Mature hypothalamus organoids contained 17 neuronal subtypes We identified seven dopaminergic neuronal subtypes in hypothalamus organoids Cell biology; Neuroscience; Stem cells research; Transcriptomics
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影响因子：
5.8
作者：
Flori E;Mastrofrancesco A;Mosca S;Ottaviani M;Briganti S;Cardinali G;Filoni A;Cameli N;Zaccarini M;Zouboulis CC;Picardo M
通讯作者：
Picardo M
DOI：
10.1073/pnas.1202526109
发表时间：
2012-09-25
影响因子：
11.1
作者：
Carter, Matthew E.;Brill, Julia;de Lecea, Luis
通讯作者：
de Lecea, Luis
影响因子：
8.8
作者：
Bartesaghi L;Wang Y;Fontanet P;Wanderoy S;Berger F;Wu H;Akkuratova N;Bouçanova F;Médard JJ;Petitpré C;Landy MA;Zhang MD;Harrer P;Stendel C;Stucka R;Dusl M;Kastriti ME;Croci L;Lai HC;Consalez GG;Pattyn A;Ernfors P;Senderek J;Adameyko I;Lallemend F;Hadjab S;Chrast R
通讯作者：
Chrast R
DOI：
10.1210/me.2012-1371
发表时间：
2013-04
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Atkin SD;Owen BM;Bookout AL;Cravo RM;Lee C;Elias CF;Elmquist JK;Kliewer SA;Mangelsdorf DJ
通讯作者：
Mangelsdorf DJ
影响因子：
5.6
作者：
Cocco C;Brancia C;Corda G;Ferri GL
通讯作者：
Ferri GL