Computational identification of key transcription factors for embryonic and postnatalSox2+dental epithelial stem cell

Abstract

ABSTRACTWhile many reptiles can replace their tooth throughout life, human loss the tooth replacement capability after formation of the permanent teeth. It was thought that the difference in tooth regeneration capability depends on the persistence of a specialized dental epithelial structure, the dental lamina that contains dental epithelial stem cells (DESC). Currently, we know very little about DESC such as what genes are expressed or its chromatin accessibility profile. Multiple markers of DESC have been proposed such asSox2andLgr5. Few single cell RNA-seq experiments have been performed previously, but no obvious DESC cluster was identified in these scRNA-seq datasets, possible due to that the expression level of DESC markers such asSox2andLgr5is too low or the percentage of DESC is too low in whole tooth. We utilize a mouse lineSox2-GFPto enrichSox2+DESC and use Smart-Seq2 protocol and ATAC-seq protocol to generate transcriptome profile and chromatin accessibility profile of P2Sox2+DESC. Additionally, we generate transcriptome profile and chromatin accessibility profile of E11.5 Sox2+ dental lamina cells. With transcriptome profile and chromatin accessibility profile, we systematically identify potential key transcription factors for E11.5Sox2+cells and P2Sox2+cells. We identified transcription factors includingPitx2, Id3, Pitx1, Tbx1, Trp63, Nkx2-3, Grhl3, Dlx2, Runx1, Nfix, Zfp536, etc potentially formed the core transcriptional regulatory networks ofSox2+DESC in both embryonic and postnatal stages.