Malhotra Gautam K, Zhao Xiangshan, Edwards Emily, Kopp Janel L, Naramura Mayumi, Sander Maike, Band Hamid, Band Vimla
Department of Genetics, Cell Biology and Anatomy, College of Medicine, University of Nebraska Medical Center, 985805 Nebraska Medical Center, Omaha, NE, 68198-5805, USA.
Departments of Pediatrics and Cellular and Molecular Medicine, University of California-San Diego, La Jolla, CA, 92093-0695, USA.
BMC Dev Biol. 2014 Dec 20;14:47. doi: 10.1186/s12861-014-0047-4.
Identification and characterization of molecular controls that regulate mammary stem and progenitor cell homeostasis are critical to our understanding of normal mammary gland development and its pathology.
We demonstrate that conditional knockout of Sox9 in the mouse mammary gland results in impaired postnatal development. In short-term lineage tracing in the postnatal mouse mammary gland using Sox9-CreER driven reporters, Sox9 marked primarily the luminal progenitors and bipotent stem/progenitor cells within the basal mammary epithelial compartment. In contrast, long-term lineage tracing studies demonstrate that Sox9+ precursors gave rise to both luminal and myoepithelial cell lineages. Finally, fate mapping of Sox9 deleted cells demonstrates that Sox9 is essential for luminal, but not myoepithelial, lineage commitment and proliferation.
These studies identify Sox9 as a key regulator of mammary gland development and stem/progenitor maintenance.
识别和表征调控乳腺干细胞和祖细胞稳态的分子调控机制对于我们理解正常乳腺发育及其病理学至关重要。
我们证明，在小鼠乳腺中条件性敲除Sox9会导致出生后发育受损。在出生后小鼠乳腺中使用Sox9-CreER驱动的报告基因进行短期谱系追踪时，Sox9主要标记乳腺基底上皮区室内的腔祖细胞和双能干细胞/祖细胞。相比之下，长期谱系追踪研究表明，Sox9+前体细胞产生了腔细胞和肌上皮细胞谱系。最后，对Sox9缺失细胞的命运图谱分析表明，Sox9对于腔细胞谱系的定向分化和增殖至关重要，但对肌上皮细胞谱系并非如此。
这些研究确定Sox9是乳腺发育和干细胞/祖细胞维持的关键调节因子。
