Sox9 regulates cell state and activity of embryonic mouse mammary progenitor cells.

Kogata, Naoko; Bland, Philip; Tsang, Mandy; Oliemuller, Erik; Lowe, Anne; Howard, Beatrice A.

Embryonic mammary cells are a unique population comprised of undifferentiated, highly plastic progenitor cells that create normal mammary tissues. The mammary gland continues to develop after birth from descendants of embryonic mammary cells. Here, we establish cell lines from mouse mammary organs, immediately after they formed during prenatal development, to facilitate studies of primitive mammary cells, which are difficult to isolate in sufficient quantities for use in functional experiments. We show that some lines can be induced to secrete milk, a distinguishing feature of mammary epithelial cells. Targeted deletion of Sox9, from one clone, decreases the ability to respond to lactogenic stimuli, consistent with a previously identified role for Sox9 in regulating luminal progenitor function. Sox9 ablation also leads to alterations in 3D morphology and downregulation of Zeb1, a key epithelial–mesenchymal transition regulator. Prenatal mammary cell lines are an invaluable resource to study regulation of mammary progenitor cell biology and development. Naoko Kogata et al. generated murine mammary progenitor cell lines that form spheres and secrete milk upon hormonal stimulation. Deletion of Sox9 increased the ability of these cells to forms spheres but decreased milk production induced by lactogenic stimuli, consistent with the role of this transcription factor on maintaining the stem cell state.

BEHAVIORAL embryology; PROGENITOR cells; MAMMARY glands; LABORATORY mice; CELL lines; PROLACTIN

Communications Biology, 2018, Vol 1, Issue 1, pN.PAG

2399-3642

Academic Journal

10.1038/s42003-018-0215-3