Development of mammary luminal progenitor cells is controlled by the transcription factor STAT5A
- Daisuke Yamaji1,
- Risu Na1,
- Yonatan Feuermann1,
- Susanne Pechhold2,
- Weiping Chen3,
- Gertraud W. Robinson1,5 and
- Lothar Hennighausen1,4
- 1Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 3Genomics Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Abstract
Mammary alveologenesis is abrogated in the absence of the transcription factors STAT5A/5B, which mediate cytokine signaling. To reveal the underlying causes for this developmental block, we studied mammary stem and progenitor cells. While loss of STAT5A/5B did not affect the stem cell population and its ability to form mammary ducts, luminal progenitors were greatly reduced and unable to form alveoli during pregnancy. Temporally controlled expression of transgenic STAT5A in mammary epithelium lacking STAT5A/5B restored the luminal progenitor population and rescued alveologenesis in a reversible fashion in vivo. Thus, STAT5A is necessary and sufficient for the establishment of luminal progenitor cells.
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Footnotes
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↵4 Corresponding authors.
E-MAIL lotharh{at}mail.nih.gov; FAX (301) 480-7312.
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↵5 E-MAIL traudl{at}nih.gov; FAX (301) 480-7312.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1840109.
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Supplemental material is available at http://www.genesdev.org.
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- Received July 6, 2009.
- Accepted September 1, 2009.
