Parity-induced mammary epithelial cells are multipotent and express cell surface markes associated with stem cells

Parity-induced mammary epithelial cells are multipotent and express cell surface markes associated with stem cells
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DOI:
10.1016/j.ydbio.2006.12.017
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发表时间:
2007-03-01
影响因子:
2.7
通讯作者:
Wagner, Kay-Uwe
Wagner, Kay-Uwe
中科院分区:
生物学3区
文献类型:
--
作者:
Matulka, Laurice A.;Triplett, Aleata A.;Wagner, Kay-Uwe

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产次诱导的乳腺上皮细胞(PI-MEC)是指在妊娠后半期和哺乳期激活晚期乳蛋白基因启动子的妊娠反应性细胞群。然而,与它们的终末分化对应物不同,这些细胞在腺体的哺乳后重塑期间不经历程序性细胞死亡。我们之前证明,移植到无上皮的乳腺脂肪垫后,PI-MEC表现出多能乳腺上皮祖细胞的两个重要特征:a)自我更新,和B)对导管和肺泡形态发生的贡献。在这份新报告中,我们介绍了一种新的方法来标记PI-MEC。使用这种方法,我们分析了卵巢激素的需求,维持这种上皮亚型在退化的乳腺。此外,我们检查了假定的干细胞标志物的表达,发现一部分GFP标记的PI-MEC是CD 24(+)/CD 49 f(高)乳腺上皮亚型的一部分,最近被认为含有多能干细胞。随后,我们证明了分离的PI-MEC能够在培养中形成乳腺球,并且在移植后,这些纯化的上皮细胞能够建立功能齐全的乳腺。这些观察结果表明,PI-MEC含有多能祖细胞,能够自我更新,并产生不同的上皮谱系存在于小鼠乳腺。(c)2006年爱思唯尔公司All rights reserved.
Parity-induced mammary epithelial cells (PI-MECs) are defined as a pregnancy hormone-responsive cell population that activates the promoter of late milk protein genes during the second half of pregnancy and lactation. However, unlike their terminally differentiated counterparts, these cells do not undergo programmed cell death during post-lactational remodeling of the gland. We previously demonstrated that upon transplantation into an epithelial-free mammary fat pad, PI-MECs exhibited two important features of multipotent mammary epithelial progenitors: a) self-renewal, and b) contribution to ductal and alveolar morphogenesis. In this new report, we introduce a new method to viably label PI-MECs. Using this methodology, we analyzed the requirement of ovarian hormones for the maintenance of this epithelial subtype in the involuted mammary gland. Furthermore, we examined the expression of putative stem cell markers and found that a portion of GFP-labeled PI-MECs were part of the CD24(+)/CD49f(high) mammary epithelial subtype, which has recently been suggested to contain multipotent stem cells. Subsequently, we demonstrated that isolated PI-MECs were able to form mammospheres in culture, and upon transplantation, these purified epithelial cells were capable of establishing a fully functional mammary gland. These observations suggest that PI-MECs contain multipotent progenitors that are able to self renew and generate diverse epithelial lineages present in the murine mammary gland. (c) 2006 Elsevier Inc. All rights reserved.