| Autor: |
Lee, Heather J., Hinshelwood, Rebecca A., Bouras, Toula, Gallego‐Ortega, David, Valdés‐Mora, Fátima, Blazek, Katrina, Visvader, Jane E., Clark, Susan J., Ormandy, Christopher J. |
| Zdroj: |
Stem Cells; October 2011, Vol. 29 Issue: 10 p1611-1619, 9p |
| Abstrakt: |
Recent characterization of mammary stem and progenitor cells has improved our understanding of the transcriptional network that coordinates mammary development; however, little is known about the mechanisms that enforce lineage commitment and prevent transdifferentiation in the mammary gland. The E‐twenty six transcription factor Elf5 forces the differentiation of mammary luminal progenitor cells to establish the milk producing alveolar lineage. Methylation of the Elf5promoter has been proposed to act as a lineage gatekeeper during embryonic development. We used bisulphite sequencing to investigate in detail whether Elf5promoter methylation plays a role in lineage commitment during mammary development. An increase in Elf5expression was associated with decreasing Elf5promoter methylation in differentiating HC11 mammary cells. Similarly, purified mammary epithelial cells from mice had increased Elf5expression and decreased promoter methylation during pregnancy. Finally, analysis of epithelial subpopulations revealed that the Elf5promoter is methylated and silenced in the basal, stem cell‐containing population relative to luminal cells. These results demonstrate that Elf5promoter methylation is lineage‐specific and developmentally regulated in the mammary gland in vivo, and suggest that loss of Elf5methylation specifies the mammary luminal lineage, while continued Elf5methylation maintains the stem cell and myoepithelial lineages. STEMCELLS2011;29:1611–1619 |
| Databáze: |
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