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

被引：5

作者：

Sarrafha, Lily ^{[1
,2
,3
]}

Neavin, Drew R.

Parfitt, Gustavo M.

Kruglikov, Ilya A. ^{[8
]}

Whitney, Kristen ^{[4
,5
,9
]}

Reyes, Ricardo ^{[1
,2
,3
]}

Coccia, Elena ^{[1
,2
,3
]}

Kareva, Tatyana ^{[1
,2
,3
]}

Goldman, Camille ^{[1
,2
,3
]}

Tipon, Regine

Croft, Gist ^{[1
,8
]}

Crary, John F. ^{[1
,4
,5
,9
,10
]}

Powell, Joseph E. ^{[7
,11
]}

Blanchard, Joel ^{[1
,3
,4
,5
,6
]}

Ahfeldt, Tim ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA

[2] Mt Sinai, Dept Neurol, New York, NY 10029 USA

[3] Icahn Sch Med Mt Sinai, Dept Cell Dev & Regenerat Biol, New York, NY 10029 USA

[4] Mt Sinai, Ronald M Loeb Ctr Alzheimers Dis, New York, NY 10029 USA

[5] Friedman Brain Inst, Mt Sinai, NY 10029 USA

[6] Mt Sinai, Black Family Stem Cell Inst, New York, NY 10029 USA

[7] Garvan Inst Med Res, Garvan Weizmann Ctr Cellular Genom, Sydney, NSW 2010, Australia

[8] New York Stem Cell Fdn, New York, NY 10019 USA

[9] Icahn Sch Med Mt Sinai, Dept Pathol Mol & Cell Based Med, New York, NY 10029 USA

[10] Windreich Dept Artificial Intelligence & Human Hlt, Mt Sinai, New York, NY 10029 USA

[11] Univ New South Wales, UNSW Cellular Genom Futures Inst, Sydney, NSW 2052, Australia

来源：

ISCIENCE | 2023年 / 26卷 / 09期

基金：

英国医学研究理事会; 澳大利亚研究理事会;

关键词：

DOPAMINERGIC-NEURONS; FUNCTIONAL NEUROANATOMY; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; IN-VITRO; GENERATION; PROLIFERATION; INITIATION; CASCADE; SYSTEM;

D O I：

10.1016/j.isci.2023.107525

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：27

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