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

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 (1)

1 LBN - Laboratoire de Bioingénierie et NanoSciences

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.

Domaines: Sciences du Vivant [q-bio]

Lejo Johnson Chacko, Hanae Lahlou, Claudia Steinacher, Said Assou, Yassine Messat, et al.. 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, 2021, 22 (19), pp.10849. ⟨10.3390/ijms221910849⟩. ⟨hal-03409973⟩