Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Florian T. Merkle; Asif Maroof; Takafumi Wataya; Yoshiki Sasai; Lorenz Studer; Kevin Eggan; Alexander F. Schier

doi:10.1242/dev.117978

journal article Feb 15, 2015

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

Florian T. Merkle Asif Maroof Takafumi Wataya Yoshiki Sasai Lorenz Studer

Kevin Eggan

Alexander F. Schier

Development Vol. 142 No. 4 pp. 633-643 · The Company of Biologists

View at Publisher Save 10.1242/dev.117978

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.

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Details

Published: Feb 15, 2015
Vol/Issue: 142(4)
Pages: 633-643

Authors

F

Florian T. Merkle

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

A

Asif Maroof

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

T

Takafumi Wataya

Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan; Department of Neurosurgery, Hospital for Sick Children, Toronto ON M5G 1X8, Canada

Y

Yoshiki Sasai

Center for Developmental Biology, RIKEN, Kobe 650-0047, Japan

L

Lorenz Studer

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

K

Kevin Eggan

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

A

Alexander F. Schier

Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA

Cite This Article

Florian T. Merkle, Asif Maroof, Takafumi Wataya, et al. (2015). Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development, 142(4), 633-643. https://doi.org/10.1242/dev.117978

Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells

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