Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell Stem Cell. 2012 Feb 3;10(2):183-97. doi: 10.1016/j.stem.2011.12.018.
Gene expression signatures relating mammary stem cell populations to breast cancers have focused on adult tissue. Here, we identify, isolate, and characterize the fetal mammary stem cell (fMaSC) state since the invasive and proliferative processes of mammogenesis resemble phases of cancer progression. fMaSC frequency peaks late in embryogenesis, enabling more extensive stem cell purification than achieved with adult tissue. fMaSCs are self-renewing, multipotent, and coexpress multiple mammary lineage markers. Gene expression, transplantation, and in vitro analyses reveal putative autocrine and paracrine regulatory mechanisms, including ErbB and FGF signaling pathways impinging on fMaSC growth. Expression profiles from fMaSCs and associated stroma exhibit significant similarities to basal-like and Her2+ intrinsic breast cancer subtypes. Our results reveal links between development and cancer and provide resources to identify new candidates for diagnosis, prognosis, and therapy.
与乳腺干细胞群体相关的基因表达特征主要集中在成人组织上。在这里，我们鉴定、分离和表征了胎儿乳腺干细胞（fMaSC）状态，因为乳腺发生的侵袭和增殖过程类似于癌症进展的阶段。fMaSC 的频率在胚胎发育后期达到峰值，使得比成人组织更能进行广泛的干细胞纯化。fMaSCs 具有自我更新、多能性，并共同表达多种乳腺谱系标志物。基因表达、移植和体外分析揭示了潜在的自分泌和旁分泌调节机制，包括影响 fMaSC 生长的 ErbB 和 FGF 信号通路。来自 fMaSCs 和相关基质的表达谱与基底样和 Her2+内在乳腺癌亚型表现出显著相似性。我们的研究结果揭示了发育和癌症之间的联系，并为鉴定新的诊断、预后和治疗候选物提供了资源。
