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 2020-03-19T09:01:02Z
dc.date.available 2020-03-19T09:01:02Z
dc.date.issued 2020-03-01
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 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
dc.identifier.other PURE: 133875548
dc.identifier.other PURE UUID: 8dd2b2bd-90a7-4385-8e76-2cfa70bc8b32
dc.identifier.other RIS: urn:59EFBD4A632E14DBD3A5018B435247C3
dc.identifier.other WOS: 000522648900002
dc.identifier.uri http://hdl.handle.net/10138/313458
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. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Disease Models & Mechanisms
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject 3111 Biomedicine
dc.subject 1184 Genetics, developmental biology, physiology
dc.subject GnRH neuron
dc.subject hPSCs
dc.subject Reporter
dc.subject Transcriptome
dc.subject ISL1
dc.subject Human
dc.subject GONADOTROPIN-RELEASING-HORMONE
dc.subject HYPOGONADOTROPIC HYPOGONADISM
dc.subject GENE-EXPRESSION
dc.subject KINASE REPRESSION
dc.subject SENSORY NEURONS
dc.subject DIFFERENTIATION
dc.subject MUTATIONS
dc.subject MIGRATION
dc.subject RECEPTOR
dc.subject GENERATION
dc.title Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells en
dc.type Article
dc.contributor.organization STEMM - Stem Cells and Metabolism Research Program
dc.contributor.organization Faculty of Medicine
dc.contributor.organization University of Helsinki
dc.contributor.organization Medicum
dc.contributor.organization Research Programs Unit
dc.contributor.organization Department of Obstetrics and Gynecology
dc.contributor.organization HUS Gynecology and Obstetrics
dc.contributor.organization Raivio Group
dc.contributor.organization Timo Pyry Juhani Otonkoski / Principal Investigator
dc.contributor.organization HUS Children and Adolescents
dc.contributor.organization Children's Hospital
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1242/dmm.040105
dc.relation.issn 1754-8403
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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