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Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells

Gifford, Casey A. and Ziller, Michael J. and Gu, Hongcang and Trapnell, Cole and Donaghey, Julie and Tsankov, Alexander and Shalek, Alex K. and Kelley, David R. and Shishkin, Alexander A. and Issner, Robbyn and Zhang, Xiaolan and Coyne, Michael and Fostel, Jennifer L. and Holmes, Laurie and Meldrim, Jim and Guttman, Mitchell and Epstein, Charles and Park, Hongkun and Kohlbacher, Oliver and Rinn, John and Gnirke, Andreas and Lander, Eric S. and Bernstein, Bradley E. and Meissner, Alexander (2013) Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells. Cell, 153 (5). pp. 1149-1163. ISSN 0092-8674. PMCID PMC3709577. https://resolver.caltech.edu/CaltechAUTHORS:20161121-130451607

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/j.cell.2013.04.037DOIArticle
http://www.sciencedirect.com/science/article/pii/S0092867413005138PublisherArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3709577/PubMed CentralArticle
ORCID:
AuthorORCID
Guttman, Mitchell0000-0003-4748-9352
Park, Hongkun0000-0001-9576-8829
Lander, Eric S.0000-0003-2662-4631
Additional Information:© 2013 Elsevier Inc. Received 17 September 2012, Revised 4 March 2013, Accepted 16 April 2013, Available online 9 May 2013. We would like to thank Kendell Clement for support of the WGBS data visualization and Loyal Goff for RNA-seq visualization, as well as Zachary Smith and Jing Liao for critical reading of the manuscript, and the SCRB FACS Core for advice regarding FACS analysis. We also thank other members of the Meissner Lab and Epigenomics Platform at the Broad Institute for helpful discussion. A.M. is supported by the Pew Charitable Trusts and is a New York Stem Cell Foundation (NYSCF) Robertson Investigator. The work was funded by the US National Institutes of Health (NIH) grants (U01ES017155 and P01GM099117) and The New York Stem Cell Foundation.
Funders:
Funding AgencyGrant Number
New York Stem Cell FoundationUNSPECIFIED
Pew Charitable TrustsUNSPECIFIED
NIHU01ES017155
NIHP01GM099117
Issue or Number:5
PubMed Central ID:PMC3709577
Record Number:CaltechAUTHORS:20161121-130451607
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20161121-130451607
Official Citation:Casey A. Gifford, Michael J. Ziller, Hongcang Gu, Cole Trapnell, Julie Donaghey, Alexander Tsankov, Alex K. Shalek, David R. Kelley, Alexander A. Shishkin, Robbyn Issner, Xiaolan Zhang, Michael Coyne, Jennifer L. Fostel, Laurie Holmes, Jim Meldrim, Mitchell Guttman, Charles Epstein, Hongkun Park, Oliver Kohlbacher, John Rinn, Andreas Gnirke, Eric S. Lander, Bradley E. Bernstein, Alexander Meissner, Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells, Cell, Volume 153, Issue 5, 23 May 2013, Pages 1149-1163, ISSN 0092-8674, http://dx.doi.org/10.1016/j.cell.2013.04.037. (http://www.sciencedirect.com/science/article/pii/S0092867413005138)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:72206
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:21 Nov 2016 23:14
Last Modified:09 Mar 2020 13:19

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