Generation of kisspeptin-responsive GnRH neurons from human pluripotent stem cells

Poliandri, A, Miller, D, Howard, S, Nobles, M, Ruiz-Babot, G, Harmer, S, Tinker, A, McKay, T, Guasti, L and Dunkel, L (2017) Generation of kisspeptin-responsive GnRH neurons from human pluripotent stem cells. Molecular and Cellular Endocrinology, 447. pp. 12-22. ISSN 0303-7207

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Official URL: http://www.elsevier.com/locate/issn/03037207

Abstract

© 2017 Elsevier B.V. GnRH neurons are fundamental for reproduction in all vertebrates, integrating all reproductive inputs. The inaccessibility of human GnRH-neurons has been a major impediment to studying the central control of reproduction and its disorders. Here, we report the efficient generation of kisspeptin responsive GnRH-secreting neurons by directed differentiation of human Embryonic Stem Cells and induced-Pluripotent Stem Cells derived from a Kallman Syndrome patient and a healthy family member. The protocol involves the generation of intermediate Neural Progenitor Cells (NPCs) through long-term Bone morphogenetic protein 4 inhibition, followed by terminal specification of these NPCs in media containing Fibroblast Growth Factor 8 and a NOTCH inhibitor. The resulting GnRH-expressing and -secreting neurons display a neuroendocrine gene expression pattern and present spontaneous calcium transients that can be stimulated by kisspeptin. These in vitro generated GnRH expressing cells provide a new resource for studying the molecular mechanisms underlying the development and function of GnRH neurons.

Item Type:	Article
Peer-reviewed:	Yes
Date Deposited:	14 Feb 2018 11:59
Publisher:	Elsevier
Additional Information:	This is an Author Accepted Manuscript of a paper accepted for publication in Molecular and Cellular Endocrinology, published by and copyright Elsevier.
Divisions:	Faculties > Science and Engineering Research Centres > Centre for Bioscience
Subject terms:	Neurons, Cell Line, Pluripotent Stem Cells, Humans, Calcium, Gene Expression Profiling, Cell Differentiation, Gene Expression Regulation, Gonadotropin-Releasing Hormone, Neural Stem Cells, Kisspeptins, Human Embryonic Stem Cells, Embryonic stem cells, GnRH neurons, Kisspeptin, Pluripotent stem cells, Calcium, Cell Differentiation, Cell Line, Gene Expression Profiling, Gene Expression Regulation, Gonadotropin-Releasing Hormone, Human Embryonic Stem Cells, Humans, Kisspeptins, Neural Stem Cells, Neurons, Pluripotent Stem Cells, 06 Biological Sciences, 11 Medical And Health Sciences, 07 Agricultural And Veterinary Sciences, Endocrinology & Metabolism
URI:	https://mmu-uat.leaf.cosector.com/id/eprint/619965
DOI:	https://doi.org/10.1016/j.mce.2017.02.030
ISSN	0303-7207

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