Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Name
Lander_Transcriptional.pdf
Size
2.84 MB
Format
Adobe PDF
Checksum (MD5)
d0dcbcd194d4d610415e9d9d63d4c1ae
Author(s)
Gifford, Casey A.
Ziller, Michael J.
Gu, Hongcang
Trapnell, Cole
Donaghey, Julie
Tsankov, Alexander
Shalek, Alex K.
Kelley, David R.
Shishkin, Alexander A.
Issner, Robbyn
Date Issued
May 2013
Journal
Cell
Publisher
Elsevier B.V.
Citation
Gifford, Casey A., Michael J. Ziller, Hongcang Gu, Cole Trapnell, Julie Donaghey, Alexander Tsankov, Alex K. Shalek, et al. “Transcriptional and Epigenetic Dynamics During Specification of Human Embryonic Stem Cells.” Cell 153, no. 5 (May 2013): 1149–1163.
Version
Final published version
Abstract
Differentiation of human embryonic stem cells (hESCs) provides a unique opportunity to study the regulatory mechanisms that facilitate cellular transitions in a human context. To that end, we performed comprehensive transcriptional and epigenetic profiling of populations derived through directed differentiation of hESCs representing each of the three embryonic germ layers. Integration of whole-genome bisulfite sequencing, chromatin immunoprecipitation sequencing, and RNA sequencing reveals unique events associated with specification toward each lineage. Lineage-specific dynamic alterations in DNA methylation and H3K4me1 are evident at putative distal regulatory elements that are frequently bound by pluripotency factors in the undifferentiated hESCs. In addition, we identified germ-layer-specific H3K27me3 enrichment at sites exhibiting high DNA methylation in the undifferentiated state. A better understanding of these initial specification events will facilitate identification of deficiencies in current approaches, leading to more faithful differentiation strategies as well as providing insights into the rewiring of human regulatory programs during cellular transitions.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2013.04.037
