| First Author | Gu B | Year | 2013 |
| Journal | Cell Stem Cell | Volume | 13 |
| Issue | 1 | Pages | 48-61 |
| PubMed ID | 23684539 | Mgi Jnum | J:199317 |
| Mgi Id | MGI:5502267 | Doi | 10.1016/j.stem.2013.04.012 |
| Citation | Gu B, et al. (2013) Chromatin effector pygo2 mediates wnt-notch crosstalk to suppress luminal/alveolar potential of mammary stem and Basal cells. Cell Stem Cell 13(1):48-61 |
| abstractText | Epigenetic mechanisms regulating lineage differentiation of mammary stem cells (MaSCs) remain poorly understood. Pygopus 2 (Pygo2) is a histone methylation reader and a context-dependent Wnt/beta-catenin coactivator. Here we provide evidence for Pygo2's function in suppressing luminal/alveolar differentiation of MaSC-enriched basal cells. We show that Pygo2-deficient MaSC/basal cells exhibit partial molecular resemblance to luminal cells, such as elevated Notch signaling and reduced mammary repopulating capability upon transplantation. Inhibition of Notch signaling suppresses basal-level and Pygo2-deficiency-induced luminal/alveolar differentiation of MaSC/basal cells, whereas activation of Wnt/beta-catenin signaling suppresses luminal/alveolar differentiation and Notch3 expression in a Pygo2-dependent manner. We show that Notch3 is a direct target of Pygo2 and that Pygo2 is required for beta-catenin binding and maintenance of a poised/repressed chromatin state at the Notch3 locus in MaSC/basal cells. Together, our data support a model where Pygo2-mediated chromatin regulation connects Wnt signaling and Notch signaling to restrict the luminal/alveolar differentiation competence of MaSC/basal cells. |
