Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells

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Lund , C , Yellapragada , V , Vuoristo , S , Balboa , D , Trova , S , Allet , C , Eskici , N , Pulli , K , Giacobini , P , Tuuri , T & Raivio , T 2020 , ' Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells ' , Disease Models & Mechanisms , vol. 13 , no. 3 , 040105 . https://doi.org/10.1242/dmm.040105

Title: Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells
Author: Lund, Carina; Yellapragada, Venkatram; Vuoristo, Sanna; Balboa, Diego; Trova, Sara; Allet, Cecile; Eskici, Nazli; Pulli, Kristiina; Giacobini, Paolo; Tuuri, Timo; Raivio, Taneli
Other contributor: University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, The Barcelona Institute of Science and Technology
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
University of Helsinki, HUS Gynecology and Obstetrics
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program










Date: 2020-03-01
Language: eng
Number of pages: 13
Belongs to series: Disease Models & Mechanisms
ISSN: 1754-8403
DOI: https://doi.org/10.1242/dmm.040105
URI: http://hdl.handle.net/10138/313458
Abstract: Gonadotropin-releasing hormone (GnRH) neurons provide a fundamental signal for the onset of puberty and subsequent reproductive functions by secretion of gonadotropin-releasing hormone. Their disrupted development or function leads to congenital hypogonadotropic hypogonadism (CHH). To model the development of human GnRH neurons, we generated a stable GNRH1-TdTomato reporter cell line in human pluripotent stem cells (hPSCs) using CRISPR-Cas9 genome editing. RNA-sequencing of the reporter clone, differentiated into GnRH neurons by dual SMAD inhibition and FGF8 treatment, revealed 6461 differentially expressed genes between progenitors and GnRH neurons. Expression of the transcription factor ISL1, one of the top 50 most upregulated genes in the TdTomato-expressing GnRH neurons, was confirmed in 10.5 gestational week-old human fetal GnRH neurons. Among the differentially expressed genes, we detected 15 genes that are implicated in CHH and several genes that are implicated in human puberty timing. Finally, FGF8 treatment in the neuronal progenitor pool led to upregulation of 37 genes expressed both in progenitors and in TdTomato-expressing GnRH neurons, which suggests upstream regulation of these genes by FGF8 signaling during GnRH neuron differentiation. These results illustrate how hPSC-derived human GnRH neuron transcriptomic analysis can be utilized to dissect signaling pathways and gene regulatory networks involved in human GnRH neuron development.This article has an associated First Person interview with the first author of the paper.
Subject: 3111 Biomedicine
1184 Genetics, developmental biology, physiology
GnRH neuron
hPSCs
Reporter
Transcriptome
ISL1
Human
GONADOTROPIN-RELEASING-HORMONE
HYPOGONADOTROPIC HYPOGONADISM
GENE-EXPRESSION
KINASE REPRESSION
SENSORY NEURONS
DIFFERENTIATION
MUTATIONS
MIGRATION
RECEPTOR
GENERATION
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