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Transcriptional and Epigenetic Dynamics during Specification of Human Embryonic Stem Cells
Open accessAbstract
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.
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“Therefore, methylation of CpG sites is an essential component of cell type-specific gene regulation, a fundamental mark of cell identity [12, 16, 41]”
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Metadata
- Authors
- Gifford, C. A., Ziller, M. J., Gu, H., Trapnell, C., Donaghey, J., Tsankov, A., Shalek, A. K., Kelley, D. R., Shishkin, A. A., Issner, R., Zhang, X., Coyne, M., Fostel, J. L., Holmes, L., Meldrim, J., Guttman, M., Epstein, C., Park, H., Kohlbacher, O., Rinn, J., Gnirke, A., Lander, E. S., Bernstein, B. E., & Meissner, A.
- Affiliations
- Broad Institute (US)
- Harvard University (US)
- Quantitative Biology Center (DE)
- Corresponding author
- Meissner, Alexander
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-05
- Volume
- 153
- Issue
- 5
- Pages
- 1149-1163
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3709577
- OpenAlex
- W2129924706
- Cited by
- 435
- References
- 61
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 22 · 2023: 17 · 2022: 22 · 2021: 38 · 2020: 28 · 2019: 36 · 2018: 31 · 2017: 40 · 2016: 48 · 2015: 61 · 2014: 51 · 2013: 18
- FWCI
- 26.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Funders
- National Institute of General Medical Sciences (P01GM099117)
- National Institute of Diabetes and Digestive and Kidney Diseases (F32DK095537)
- National Institute of Environmental Health Sciences (U01ES017155)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- human embryonic stem cells, directed differentiation, germ layer specification, DNA methylation, H3K4me1, H3K27me3, distal regulatory elements, pluripotency factors, chromatin regulation, epigenetic regulation, transcriptional regulation
- MeSH terms
- Acetylation, Cell Differentiation, Chromatin, Enhancer Elements, Genetic, Histones, Humans, Methylation, Transcription, Genetic, DNA Methylation, Epigenesis, Genetic, Embryonic Stem Cells
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