Identification and Massively Parallel Characterization of Regulatory Elements Driving Neural Induction
Cell Stem Cell. 2019-11-07;25(5):713-727.e10.
- Abstract
- 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.
- Consortium data used in this publication
- The datasets generated during this study are available at the NCBI Gene Expression Omnibus (GEO) as accession number GEO: GSE115046. The published article includes all code generated or analyzed during this study. GSE115043 -- Massively parallel characterization of regulatory dynamics during neural induction [ChIP-seq]; GSE115044 -- Massively parallel characterization of regulatory dynamics during neural induction [ATAC-seq]; GSE115045--Massively parallel characterization of regulatory dynamics during neural induction [RNA-seq]; GSE134678--Massively parallel characterization of regulatory dynamics during neural induction [RNA-seq II]
- Datasets
- DSR630CRR, DSR082DUO, DSR302JLO, DSR254TDC, DSR527GBV, DSR396BPY, DSR317ZPB, DSR530WUY, DSR086PWQ, DSR344CNS, DSR698ICY, DSR737FOC, DSR291TNO, DSR024BHI, DSR871DNT, DSR866WER, DSR143SDR, DSR756KXQ, DSR709XQF, DSR220MQJ, DSR670TFL, DSR371THL, DSR155WBN, DSR345ZVY, DSR331BUU, DSR330WXD, DSR604WQE, DSR877AGW, DSR853VKZ, DSR270XTH, DSR499QKH, DSR711EXK, DSR360AYV, DSR287XNF, DSR597KKS, DSR689USA, DSR899SXW, DSR551CTK, DSR033SYZ, DSR457EIN, DSR853VRX, DSR778XLT, DSR454HRG, DSR936UCL, DSR307PEB, DSR143FTF, DSR869PNN, DSR142ZGJ, DSR753TLG, DSR975ZRS, DSR874DKL, DSR915CWS, DSR909HZA, DSR515AMY, DSR796WZS, DSR514DMD, DSR850QZK, DSR680UFD, DSR802YPG, DSR364LGY, DSR025IHE, DSR816HWX, DSR807LBJ, DSR132ZEI, DSR884KZR, DSR546TDD, DSR625SNC, DSR497PVP, DSR941EJT, DSR375AUB, DSR299TWX, DSR041LET, DSR505QBO, DSR339BEW, DSR726PAN, DSR046ETP, DSR173SDV, DSR147MAT, DSR016YHI, DSR593HJU, DSR329IUZ, DSR591JXV, DSR876LOS, DSR045TKK, DSR409KBC