title: Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells.
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.
authors: 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.
authors: Florian T
authors: FT
authors: Merkle
authors: 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.
authors: Asif
authors: A
authors: Maroof
authors: Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan Department of Neurosurgery, Hospital for Sick Children, Toronto ON M5G 1X8, Canada.
authors: Takafumi
authors: T
authors: Wataya
authors: Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan.
authors: Yoshiki
authors: Y
authors: Sasai
authors: 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.
authors: Lorenz
authors: L
authors: Studer
authors: 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.
authors: Kevin
authors: K
authors: Eggan
authors: 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.
authors: Alexander F
authors: AF
authors: Schier
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D006801:Humans; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D010121:Oxytocin / Q000378:metabolism; D010907:Pituitary Hormones / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
chemical_list: D054369:Agouti-Related Protein; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D001127:Arginine Vasopressin; D010121:Oxytocin; D013973:Thyrotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; C019463:melanin-concentrating hormone
keywords: Differentiation; Human; Hypothalamus; Mouse; Narcolepsy; Neuropeptide; Pluripotent; Stem cell