Neurod1 intrinsically initiates differentiation of induced pluripotent stem cells into neural progenitor cells

Won Young Choi, Ji Hyun Hwang, Ann Na Cho, Andrew J. Lee, Inkyung Jung, Seung Woo Cho, Lark Kyun Kim, Young Joon Kim

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1011-1022
Number of pages12
JournalMolecules and cells
Volume43
Issue number12
DOIs
Publication statusPublished - 2020

Bibliographical note

Funding Information:
This work was supported by Samsung Science and Technology Foundation Project (SSTF-BA1601-13).

Publisher Copyright:
© The Korean Society for Molecular and Cellular Biology. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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