Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs

We analyzed transcriptomic data from otic sensory cells differentiated from human induced pluripotent stem cells (hiPSCs) by a previously described method to gain new insights into the early human otic neurosensory lineage. We identified genes and biological networks not previously described to occu...

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Main Authors: Lejo Johnson Chacko, Hanae Lahlou, Claudia Steinacher, Said Assou, Yassine Messat, József Dudás, Albert Edge, Berta Crespo, Moira Crosier, Consolato Sergi, Anneliese Schrott-Fischer, Azel Zine
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/19/10849
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author Lejo Johnson Chacko
Hanae Lahlou
Claudia Steinacher
Said Assou
Yassine Messat
József Dudás
Albert Edge
Berta Crespo
Moira Crosier
Consolato Sergi
Anneliese Schrott-Fischer
Azel Zine
author_facet Lejo Johnson Chacko
Hanae Lahlou
Claudia Steinacher
Said Assou
Yassine Messat
József Dudás
Albert Edge
Berta Crespo
Moira Crosier
Consolato Sergi
Anneliese Schrott-Fischer
Azel Zine
author_sort Lejo Johnson Chacko
collection DOAJ
description We analyzed transcriptomic data from otic sensory cells differentiated from human induced pluripotent stem cells (hiPSCs) by a previously described method to gain new insights into the early human otic neurosensory lineage. We identified genes and biological networks not previously described to occur in the human otic sensory developmental cell lineage. These analyses identified and ranked genes known to be part of the otic sensory lineage program (SIX1, EYA1, GATA3, etc.), in addition to a number of novel genes encoding extracellular matrix (ECM) (COL3A1, COL5A2, DCN, etc.) and integrin (ITG) receptors (ITGAV, ITGA4, ITGA) for ECM molecules. The results were confirmed by quantitative PCR analysis of a comprehensive panel of genes differentially expressed during the time course of hiPSC differentiation in vitro. Immunocytochemistry validated results for select otic and ECM/ITG gene markers in the in vivo human fetal inner ear. Our screen shows ECM and ITG gene expression changes coincident with hiPSC differentiation towards human otic neurosensory cells. Our findings suggest a critical role of ECM-ITG interactions with otic neurosensory lineage genes in early neurosensory development and cell fate determination in the human fetal inner ear.
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spelling doaj.art-d084fb36f922445c9a2cfb599abbba5c2023-11-22T16:16:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122191084910.3390/ijms221910849Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCsLejo Johnson Chacko0Hanae Lahlou1Claudia Steinacher2Said Assou3Yassine Messat4József Dudás5Albert Edge6Berta Crespo7Moira Crosier8Consolato Sergi9Anneliese Schrott-Fischer10Azel Zine11Inner Ear Laboratory, Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, AustriaHarvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02101, USAInner Ear Laboratory, Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, AustriaIRMB, Univ Montpellier, INSERM, CHU Montpellier, 34000 Montpellier, FranceLBN, Laboratory of Bioengineering and Nanoscience, Univ Montpellier, 34090 Montpellier, FranceInner Ear Laboratory, Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, AustriaHarvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02101, USAUCL Great Ormond Street Institute of Child Health, University College London, London WC1 N1EH, UKHuman Development Biology Resource, Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle NE1 4EP, UKAnatomic Pathology Division, Children’s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, CanadaInner Ear Laboratory, Department of Otorhinolaryngology, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, AustriaLBN, Laboratory of Bioengineering and Nanoscience, Univ Montpellier, 34090 Montpellier, FranceWe analyzed transcriptomic data from otic sensory cells differentiated from human induced pluripotent stem cells (hiPSCs) by a previously described method to gain new insights into the early human otic neurosensory lineage. We identified genes and biological networks not previously described to occur in the human otic sensory developmental cell lineage. These analyses identified and ranked genes known to be part of the otic sensory lineage program (SIX1, EYA1, GATA3, etc.), in addition to a number of novel genes encoding extracellular matrix (ECM) (COL3A1, COL5A2, DCN, etc.) and integrin (ITG) receptors (ITGAV, ITGA4, ITGA) for ECM molecules. The results were confirmed by quantitative PCR analysis of a comprehensive panel of genes differentially expressed during the time course of hiPSC differentiation in vitro. Immunocytochemistry validated results for select otic and ECM/ITG gene markers in the in vivo human fetal inner ear. Our screen shows ECM and ITG gene expression changes coincident with hiPSC differentiation towards human otic neurosensory cells. Our findings suggest a critical role of ECM-ITG interactions with otic neurosensory lineage genes in early neurosensory development and cell fate determination in the human fetal inner ear.https://www.mdpi.com/1422-0067/22/19/10849human induced pluripotent stem cellsotic sensory progenitorsgene expression analysisextracellular matrixintegrinshuman fetal inner ear
spellingShingle Lejo Johnson Chacko
Hanae Lahlou
Claudia Steinacher
Said Assou
Yassine Messat
József Dudás
Albert Edge
Berta Crespo
Moira Crosier
Consolato Sergi
Anneliese Schrott-Fischer
Azel Zine
Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
International Journal of Molecular Sciences
human induced pluripotent stem cells
otic sensory progenitors
gene expression analysis
extracellular matrix
integrins
human fetal inner ear
title Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
title_full Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
title_fullStr Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
title_full_unstemmed Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
title_short Transcriptome-Wide Analysis Reveals a Role for Extracellular Matrix and Integrin Receptor Genes in Otic Neurosensory Differentiation from Human iPSCs
title_sort transcriptome wide analysis reveals a role for extracellular matrix and integrin receptor genes in otic neurosensory differentiation from human ipscs
topic human induced pluripotent stem cells
otic sensory progenitors
gene expression analysis
extracellular matrix
integrins
human fetal inner ear
url https://www.mdpi.com/1422-0067/22/19/10849
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