Journal
CELL REPORTS
Volume 15, Issue 6, Pages 1359-1368Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.04.020
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Funding
- CREST, JST
- Japanese Society for the Promotion of Science (JSPS) KAKENHI Grant [24615004, 23390404]
- Core Center for iPS Cell Research, Research Center Network for Realization of Regenerative Medicine from Japan Agency for Medical Research and Development, AMED
- iPS Cell Research Fund
- Funding Program for World-Leading Innovative Research and Development on Science and Technology (FIRST Program) of JSPS
- Grants-in-Aid for Scientific Research [15J04853, 24615004, 15K21113, 23390404] Funding Source: KAKEN
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In development, embryonic ectoderm differentiates into neuroectoderm and surface ectoderm using poorly understood mechanisms. Here, we show that the transcription factor OVOL2 maintains the transcriptional program of human corneal epithelium cells (CECs), a derivative of the surface ectoderm, and that OVOL2 may regulate the differential transcriptional programs of the two lineages. A functional screen identified OVOL2 as a repressor of mesenchymal genes to maintain CECs. Transduction of OVOL2 with several other transcription factors induced the transcriptional program of CECs in fibroblasts. Moreover, neuroectoderm derivatives were found to express mesenchymal genes, and OVOL2 alone could induce the transcriptional program of CECs in neural progenitors by repressing these genes while activating epithelial genes. Our data suggest that the difference between the transcriptional programs of some neuroectoderm-and surface ectoderm-derivative cells may be regulated in part by a reciprocally repressive mechanism between epithelial and mesenchymal genes, as seen in epithelial-to-mesenchymal transition.
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