s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue
s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue
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DOI：
10.1101/gad.1932810
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发表时间：
2010-09-10
影响因子：
10.5
通讯作者：
Rohrschneider, Larry R.
中科院分区：
文献类型：
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作者：
Bai, Lixia;Rohrschneider, Larry R.
乳腺干细胞（MaSC）在乳腺的正常发育甚至肿瘤发生中发挥着关键作用。使用组合细胞标记，成体 MaSC 已在基底细胞群中富集，但 MaSC 的确切身份仍然未知。我们使用 s-SHIP 启动子在转基因小鼠模型的胚胎中用 GFP 标记假定的干细胞。在这里，我们发现，在出生后乳腺发育中，青春期的 GFP(+) 帽细胞和妊娠期的基底肺泡芽细胞在移植后均表现出新功能性乳腺的所有乳腺上皮细胞的自我更新和再生能力。单个 GFP(+) 细胞可以再生乳腺上皮网络。 GFP(+)乳腺上皮细胞为p63(+)、CD24(mod)、CD49f(high)和CD29(high)；正在积极增殖；并表达 s-SHIP mRNA。总体而言，我们的结果确定了体内激活的 MaSC 群体处于乳腺中快速发育的终末芽（青春期）和肺泡芽（怀孕）的最前沿。此外，GFP(+)基底细胞在MMTV-Wnt1乳腺肿瘤中扩增，但在ErbB2肿瘤中不扩增。这些结果使得能够使用新的小鼠模型通过一致的单一参数进行MaSC原位识别和分离，并应用于进一步分析正常和潜在的癌症干细胞。
Mammary stem cells (MaSCs) play critical roles in normal development and perhaps tumorigenesis of the mammary gland. Using combined cell markers, adult MaSCs have been enriched in a basal cell population, but the exact identity of MaSCs remains unknown. We used the s-SHIP promoter to tag presumptive stem cells with GFP in the embryos of a transgenic mouse model. Here we show, in postnatal mammary gland development, that GFP(+) cap cells in puberty and basal alveolar bud cells in pregnancy each exhibit self-renewal and regenerative capabilities for all mammary epithelial cells of a new functional mammary gland upon transplantation. Single GFP(+) cells can regenerate the mammary epithelial network. GFP(+) mammary epithelial cells are p63(+), CD24(mod), CD49f(high), and CD29(high); are actively proliferating; and express s-SHIP mRNA. Overall, our results identify the activated MaSC population in vivo at the forefront of rapidly developing terminal end buds (puberty) and alveolar buds (pregnancy) in the mammary gland. In addition, GFP(+) basal cells are expanded in MMTV-Wnt1 breast tumors but not in ErbB2 tumors. These results enable MaSC in situ identification and isolation via a consistent single parameter using a new mouse model with applications for further analyses of normal and potential cancer stem cells.