Abstract
Differentiation is an epigenetic program that involves the gradual loss of pluripotency and acquisition of cell type–specific features. Understanding these processes requires genome-wide analysis of epigenetic and gene expression profiles, which have been challenging in primary tissue samples due to limited numbers of cells available. Here we describe the application of high-throughput sequencing technology for profiling histone and DNA methylation, as well as gene expression patterns of normal human mammary progenitor-enriched and luminal lineage-committed cells. We observed significant differences in histone H3 lysine 27 tri-methylation (H3K27me3) enrichment and DNA methylation of genes expressed in a cell type–specific manner, suggesting their regulation by epigenetic mechanisms and a dynamic interplay between the two processes that together define developmental potential. The technologies we developed and the epigenetically regulated genes we identified will accelerate the characterization of primary cell epigenomes and the dissection of human mammary epithelial lineage-commitment and luminal differentiation.
Highlights
Cellular differentiation is a well-orchestrated epigenetic program by which the developmental potential of the cells is progressively restricted
The list of genes epigenetically regulated in a cell type–specific manner provides a rich resource for the further analysis of human breast development and the role of epigenetic mechanisms in breast tumorigenesis
CD24+ and progenitor-enriched CD44+ breast epithelial cells at the molecular level, we isolated these cells from normal breast tissue and analyzed their comprehensive gene expression profiles and clonogenicity [16,17]
Summary
Cellular differentiation is a well-orchestrated epigenetic program by which the developmental potential of the cells is progressively restricted. In adult tissues reversal of such programs is rarely observed with the exception of tissue regeneration, metaplasia, and neoplastic transformation. With the iPS (induced pluripotent stem cells) technology, directed cellular reprogramming is becoming a reality with wide implications in human disease [1]. The successful application of this technology requires the accurate understanding of cell type–specific epigenetic regulatory programs that depend on DNA methylation, chromatin (histone) modification, and non-coding RNAs. The successful application of this technology requires the accurate understanding of cell type–specific epigenetic regulatory programs that depend on DNA methylation, chromatin (histone) modification, and non-coding RNAs Each of these mechanisms has been shown to play a role in regulating stem cell function and differentiation, as well as tumorigenesis and they have been extensively studied in embryonic stem cells (ESCs). The genome-wide chromatin and DNA methylation patterns of human adult tissue-specific stem cells (ASCs) have not been explored
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