論文

査読有り
2019年11月7日

Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction

Cell Stem Cell
  • Fumitaka Inoue
  • ,
  • Anat Kreimer
  • ,
  • Tal Ashuach
  • ,
  • Nadav Ahituv
  • ,
  • Nir Yosef

担当区分
筆頭著者
25
5
開始ページ
713
終了ページ
727.e10
DOI
10.1016/j.stem.2019.09.010

© 2019 Elsevier Inc. Epigenomic regulation and lineage-specific gene expression act in concert to drive cellular differentiation, but the temporal interplay between these processes is largely unknown. Using neural induction from human pluripotent stem cells (hPSCs) as a paradigm, we interrogated these dynamics by performing RNA sequencing (RNA-seq), chromatin immunoprecipitation sequencing (ChIP-seq), and assay for transposase accessible chromatin using sequencing (ATAC-seq) at seven time points during early neural differentiation. We found that changes in DNA accessibility precede H3K27ac, which is followed by gene expression changes. Using massively parallel reporter assays (MPRAs) to test the activity of 2,464 candidate regulatory sequences at all seven time points, we show that many of these sequences have temporal activity patterns that correlate with their respective cell-endogenous gene expression and chromatin changes. A prioritization method incorporating all genomic and MPRA data further identified key transcription factors involved in driving neural fate. These results provide a comprehensive resource of genes and regulatory elements that orchestrate neural induction and illuminate temporal frameworks during differentiation.

リンク情報
DOI
https://doi.org/10.1016/j.stem.2019.09.010
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/31631012
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850896
URL
http://europepmc.org/abstract/med/31631012
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85074269503&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85074269503&origin=inward

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