title: Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.
abstract: The hypothalamus comprises neuronal clusters that are essential for body weight regulation and other physiological functions. Insights into the complex cellular physiology of this region of the brain are critical to understanding the pathogenesis of obesity, but human hypothalamic cells are largely inaccessible for direct study. Here we describe a technique for generation of arcuate-like hypothalamic neurons from human pluripotent stem (hPS) cells. Early activation of SHH signaling and inhibition of BMP and TGFβ signaling, followed by timed inhibition of NOTCH, can efficiently differentiate hPS cells into NKX2.1+ hypothalamic progenitors. Subsequent incubation with BDNF induces the differentiation and maturation of pro-opiomelanocortin and neuropeptide Y neurons, which are major cell types in the arcuate hypothalamus. These neurons have molecular and cellular characteristics consistent with arcuate neurons. © 2016 by John Wiley & Sons, Inc.
authors.affiliation: Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York.|Division of Molecular Genetics, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Liheng
authors.initials: L
authors.lastname: Wang
authors.affiliation: Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York.|Division of Molecular Genetics, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.|New York Stem Cell Foundation Research Institute, New York, New York.
authors.forename: Dieter
authors.initials: D
authors.lastname: Egli
authors.affiliation: Naomi Berrie Diabetes Center, Columbia University College of Physicians and Surgeons, New York, New York.|Division of Molecular Genetics, Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Leibel
mesh_terms: D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D002454:Cell Differentiation; D006801:Humans; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y; D011333:Pro-Opiomelanocortin
keywords: ARC neurons; feeder-free; human pluripotent stem cells; hypothalamic neurons