Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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NEUROD1 Intrinsically Initiates Differentiation of Induced Pluripotent Stem Cells into Neural Progenitor Cells

  • Choi, Won-Young (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Hwang, Ji-Hyun (Interdisciplinary Program of Integrated OMICS for Biomedical Science, The Graduate School, Yonsei University) ;
  • Cho, Ann-Na (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Lee, Andrew J. (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Jung, Inkyung (Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Cho, Seung-Woo (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Kim, Lark Kyun (Severance Biomedical Science Institute and BK21 PLUS Project for Medical Sciences, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Kim, Young-Joon (Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University)
  • Received : 2020.10.21
  • Accepted : 2020.11.16
  • Published : 2020.12.31
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Abstract

Cell type specification is a delicate biological event in which every step is under tight regulation. From a molecular point of view, cell fate commitment begins with chromatin alteration, which kickstarts lineage-determining factors to initiate a series of genes required for cell specification. Several important neuronal differentiation factors have been identified from ectopic over-expression studies. However, there is scarce information on which DNA regions are modified during induced pluripotent stem cell (iPSC) to neuronal progenitor cell (NPC) differentiation, the cis regulatory factors that attach to these accessible regions, or the genes that are initially expressed. In this study, we identified the DNA accessible regions of iPSCs and NPCs via the Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq). We identified which chromatin regions were modified after neuronal differentiation and found that the enhancer regions had more active histone modification changes than the promoters. Through motif enrichment analysis, we found that NEUROD1 controls iPSC differentiation to NPC by binding to the accessible regions of enhancers in cooperation with other factors such as the Hox proteins. Finally, by using Hi-C data, we categorized the genes that directly interacted with the enhancers under the control of NEUROD1 during iPSC to NPC differentiation.

Keywords

References

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