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Development. 2015 Feb 15;142(4):633-43. doi: 10.1242/dev.117978.

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.

Author information

1
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA.
2
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA.
3
Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan Department of Neurosurgery, Hospital for Sick Children, Toronto ON M5G 1X8, Canada.
4
Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
5
The Center for Stem Cell Biology, Sloan-Kettering Institute for Cancer Research, New York, NY 10065, USA Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, NY 10065, USA.
6
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA 02138, USA keggan@scrb.harvard.edu schier@fas.harvard.edu.
7
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA keggan@scrb.harvard.edu schier@fas.harvard.edu.

Abstract

Hypothalamic neurons orchestrate many essential physiological and behavioral processes via secreted neuropeptides, and are relevant to human diseases such as obesity, narcolepsy and infertility. We report the differentiation of human pluripotent stem cells into many of the major types of neuropeptidergic hypothalamic neurons, including those producing pro-opiolemelanocortin, agouti-related peptide, hypocretin/orexin, melanin-concentrating hormone, oxytocin, arginine vasopressin, corticotropin-releasing hormone (CRH) or thyrotropin-releasing hormone. Hypothalamic neurons can be generated using a 'self-patterning' strategy that yields a broad array of cell types, or via a more reproducible directed differentiation approach. Stem cell-derived human hypothalamic neurons share characteristic morphological properties and gene expression patterns with their counterparts in vivo, and are able to integrate into the mouse brain. These neurons could form the basis of cellular models, chemical screens or cellular therapies to study and treat common human diseases.

KEYWORDS:

Differentiation; Human; Hypothalamus; Mouse; Narcolepsy; Neuropeptide; Pluripotent; Stem cell

PMID:
25670790
PMCID:
PMC4325380
DOI:
10.1242/dev.117978
[Indexed for MEDLINE]
Free PMC Article

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