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

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• dc.contributor.author Lund, Carina
• dc.contributor.author Yellapragada, Venkatram
• dc.contributor.author Vuoristo, Sanna
• dc.contributor.author Balboa, Diego
• dc.contributor.author Trova, Sara
• dc.contributor.author Allet, Cecile
• dc.contributor.author Eskici, Nazli
• dc.contributor.author Pulli, Kristiina
• dc.contributor.author Giacobini, Paolo
• dc.contributor.author Tuuri, Timo
• dc.contributor.author Raivio, Taneli
• dc.date.accessioned 2020-11-18T07:04:48Z
• dc.date.available 2020-11-18T07:04:48Z
• dc.date.issued 2020
• dc.description.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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Lund C, Yellapragada V, Vuoristo S, Balboa D, Trova S, Allet C, Eskici N, Pulli K, Giacobini P, Tuuri T, Raivio T. Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells. Dis Model Mech. 2020; 13(3):dmm040105. DOI: 10.1242/dmm.040105
• dc.identifier.doi http://dx.doi.org/10.1242/dmm.040105
• dc.identifier.issn 1754-8403
• dc.identifier.uri http://hdl.handle.net/10230/45794
• dc.language.iso eng
• dc.publisher Company of Biologists
• dc.relation.ispartof Dis Model Mech. 2020; 13(3):dmm040105
• dc.rights © 2020. Published by The Company of Biologists Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri https://creativecommons.org/licenses/by/4.0
• dc.subject.keyword GnRH neuron
• dc.subject.keyword Human
• dc.subject.keyword ISL1
• dc.subject.keyword Reporter
• dc.subject.keyword Transcriptome
• dc.subject.keyword hPSCs
• dc.title Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion