Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells

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Lund , C , Pulli , A K , Yellapragada , V , Giacobini , P , Lundin (Stenroos) , K , Vuoristo , S , Tuuri , T , Noisa , P & Raivio , T 2016 , ' Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells ' , Stem cell reports , vol. 7 , no. 2 , pp. 149-157 . https://doi.org/10.1016/j.stemcr.2016.06.007

Title: Development of Gonadotropin-Releasing Hormone-Secreting Neurons from Human Pluripotent Stem Cells
Author: Lund, Carina; Pulli, Aino Kristiina; Yellapragada, Venkatram; Giacobini, Paolo; Lundin (Stenroos), Karolina; Vuoristo, Sanna; Tuuri, Timo; Noisa, Parinya; Raivio, Taneli
Contributor: University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Medicum
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, Medicum
University of Helsinki, Medicum
Date: 2016-08-09
Language: eng
Number of pages: 9
Belongs to series: Stem cell reports
ISSN: 2213-6711
URI: http://hdl.handle.net/10138/167151
Abstract: Gonadotropin-releasing hormone (GnRH) neurons regulate human puberty and reproduction. Modeling their development and function in vitro would be of interest for both basic research and clinical translation. Here, we report a three-step protocol to differentiate human pluripotent stem cells (hPSCs) into GnRH-secreting neurons. Firstly, hPSCs were differentiated to FOXG1, EMX2, and PAX6 expressing anterior neural progenitor cells (NPCs) by dual SMAD inhibition. Secondly, NPCs were treated for 10 days with FGF8, which is a key ligand implicated in GnRH neuron ontogeny, and finally, the cells were matured with Notch inhibitor to bipolar TUJ1-positive neurons that robustly expressed GNRH1 and secreted GnRH decapeptide into the culture medium. The protocol was reproducible both in human embryonic stem cells and induced pluripotent stem cells, and thus provides a translational tool for investigating the mechanisms of human puberty and its disorders.
Subject: OLFACTORY PLACODE
GNRH NEURONS
NEURAL CREST
CRANIAL PLACODES
PROGENITOR CELLS
IN-VIVO
DIFFERENTIATION
MOUSE
EXPRESSION
SYSTEM
1182 Biochemistry, cell and molecular biology
3123 Gynaecology and paediatrics
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