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bioRxiv · 10.1101/2024.10.08.617209

EPHA2 Regulates SOX2 during Esophageal Development

Li, T.·Mitani, Y.·Cruz-Acuna, R.·Karaksheva, T. A.·Sahu, V.·Martin, C.·Nakagawa, H.·Gabre, J.
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Abstract

The human esophagus, derived from the anterior foregut endoderm, requires proper dorsal-ventral patterning for development. The transcription factor SOX2, crucial in this process, when dysregulated, leads to congenital esophageal abnormalities. EPHA2, a receptor tyrosine kinase, is vital in various developmental processes and cancer models, where it activates SOX2. This study demonstrates that EPHA2 regulates SOX2 expression during esophageal development using human iPSCs and iPSC-derived human esophageal organoids (HEO). Inhibition of EPHA2 decreased iPSC-derived HEO formation and SOX2 expression. These findings provide evidence of EPHA2 as being a key regulator of SOX2 signaling in early esophageal development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/617209v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@16b8a8aorg.highwire.dtl.DTLVardef@1548672org.highwire.dtl.DTLVardef@46e28corg.highwire.dtl.DTLVardef@1c35578_HPS_FORMAT_FIGEXP M_FIG SFD: Serum-Free Differentiation media; EPC: esophageal progenitor cells; HEO: human esophageal organoids Created with BioRender.com C_FIG HighlightsO_LISOX2 is crucial for proper esophageal development. C_LIO_LIEPHA2 is a receptor tyrosine kinase involved in various developmental processes. C_LIO_LIEPHA2 activates SOX2. C_LIO_LIInhibition of EPHA2 decreased SOX2 expression and human esophageal organoid formation. C_LI

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Li, T., Mitani, Y., Cruz-Acuna, R., Karaksheva, T. A., Sahu, V., Martin, C., Nakagawa, H., Gabre, J.. 2024-10-10. EPHA2 Regulates SOX2 during Esophageal Development. https://doi.org/10.1101/2024.10.08.617209

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