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dc.contributor.authorBloushtain-Qimron, Noga
dc.contributor.authorYao, Jun
dc.contributor.authorSnyder, Eric L.
dc.contributor.authorShipitsin, Michail
dc.contributor.authorCampbell, Lauren L.
dc.contributor.authorMani, Sendurai A.
dc.contributor.authorHu, Min
dc.contributor.authorChen, Haiyan
dc.contributor.authorUstyansky, Vadim
dc.contributor.authorAntosiewicz, Jessica E.
dc.contributor.authorArgani, Pedram
dc.contributor.authorHalushka, Marc K.
dc.contributor.authorThomson, James A.
dc.contributor.authorPharoah, Paul
dc.contributor.authorPorgador, Angel
dc.contributor.authorSukumar, Saraswati
dc.contributor.authorParsons, Ramon
dc.contributor.authorRichardson, Andrea L.
dc.contributor.authorStampfer, Martha R.
dc.contributor.authorGelman, Rebecca S.
dc.contributor.authorNikolskaya, Tatiana
dc.contributor.authorNikolsky, Yuri
dc.contributor.authorPolyak, Kornelia
dc.date.accessioned2019-09-06T14:15:06Z
dc.date.issued2008
dc.identifier.citationBloushtain-Qimron, N., J. Yao, E. L. Snyder, M. Shipitsin, L. L. Campbell, S. A. Mani, M. Hu, et al. 2008. “Cell Type-Specific DNA Methylation Patterns in the Human Breast.” Proceedings of the National Academy of Sciences 105 (37): 14076–81. https://doi.org/10.1073/pnas.0805206105.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41292848*
dc.description.abstractCellular identity and differentiation are determined by epigenetic programs. The characteristics of these programs in normal human mammary epithelium and their similarity to those in stem cells are unknown. To begin investigating these issues, we analyzed the DNA methylation and gene expression profiles of distinct subpopulations of mammary epithelial cells by using MSDK (methylation-specific digital karyotyping) and SAGE (serial analysis of gene expression). We identified discrete cell-type and differentiation state-specific DNA methylation and gene expression patterns that were maintained in a subset of breast carcinomas and correlated with clinically relevant tumor subtypes. CD44+ cells were the most hypomethylated and highly expressed several transcription factors with known stem cell function including HOXA10 and TCF3. Many of these genes were also hypomethylated in BMP4-treated compared with undifferentiated human embryonic stem (ES) cells that we analyzed by MSDK for comparison. Further highlighting the similarity of epigenetic programs of embryonic and mammary epithelial cells, genes highly expressed in CD44+ relative to more differentiated CD24+ cells were significantly enriched for Suz12 targets in ES cells. The expression of FOXC1, one of the transcription factors hypomethylated and highly expressed in CD44+ cells, induced a progenitor-like phenotype in differentiated mammary epithelial cells. These data suggest that epigenetically controlled transcription factors play a key role in regulating mammary epithelial cell phenotypes and imply similarities among epigenetic programs that define progenitor cell characteristics.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleCell type-specific DNA methylation patterns in the human breast
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorStampfer, Meir
dc.date.available2019-09-06T14:15:06Z
dash.workflow.comments1Science Serial ID 90187
dc.identifier.doi10.1073/pnas.0805206105
dash.source.volume105;37
dash.source.page14076


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