Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules.
Anatomical localization of progenitor cells in human breast tissue reveals enrichment of uncommitted cells within immature lobules.
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DOI：
10.1186/s13058-014-0453-3
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发表时间：
2014-10-15
期刊：
影响因子：
--
通讯作者：
Kuperwasser C
中科院分区：
文献类型：
--
作者：
Arendt LM;Keller PJ;Skibinski A;Goncalves K;Naber SP;Buchsbaum RJ;Gilmore H;Come SE;Kuperwasser C
小鼠谱系追踪研究揭示了谱系限制性乳腺上皮祖细胞的定位和存在，其在功能上有助于青春期的扩张性生长和妊娠期的分化。然而，小鼠和人类乳腺组织之间广泛的解剖学差异排除了将啮齿动物发现直接转化为人类乳腺的可能性。因此，在这里，我们表征乳腺祖细胞层次结构，并确定人体乳腺组织内的祖细胞的解剖位置。从无病乳房缩小术组织中分离乳腺上皮细胞（MEC），并在体外和体内测定干/祖细胞活性。对MEC进行分选并评价其在胶原蛋白上的生长和谱系标志物的表达。乳腺小叶进行显微解剖，并根据谱系标志物和类固醇受体表达单独表征，以确定祖细胞的解剖位置。使用密度标准化事件生成树进展分析（SPADE）从高维细胞术数据中识别小叶内MEC的细胞层次结构。综合多种祖细胞活性测定，我们确定了腔肺泡和基底导管祖细胞的存在。此外，我们表明，I型小叶的人乳房是最不成熟的，表现出不受限制的模式表达的管腔和基底谱系标记。与此一致，SPADE分析显示，未成熟的小叶富含基底祖细胞，而成熟的小叶由管腔谱系内细胞层次复杂性增加组成。这些结果揭示了人类乳腺上皮层次结构的潜在差异，并表明随着腺体成熟度的增加，上皮层次结构也变得更加复杂。本文的在线版本（doi：10.1186/s13058-014-0453-3）包含补充材料，可供授权用户使用。
Lineage tracing studies in mice have revealed the localization and existence of lineage-restricted mammary epithelial progenitor cells that functionally contribute to expansive growth during puberty and differentiation during pregnancy. However, extensive anatomical differences between mouse and human mammary tissues preclude the direct translation of rodent findings to the human breast. Therefore, here we characterize the mammary progenitor cell hierarchy and identify the anatomic location of progenitor cells within human breast tissues. Mammary epithelial cells (MECs) were isolated from disease-free reduction mammoplasty tissues and assayed for stem/progenitor activity in vitro and in vivo. MECs were sorted and evaluated for growth on collagen and expression of lineages markers. Breast lobules were microdissected and individually characterized based on lineage markers and steroid receptor expression to identify the anatomic location of progenitor cells. Spanning-tree progression analysis of density-normalized events (SPADE) was used to identify the cellular hierarchy of MECs within lobules from high-dimensional cytometry data. Integrating multiple assays for progenitor activity, we identified the presence of luminal alveolar and basal ductal progenitors. Further, we show that Type I lobules of the human breast were the least mature, demonstrating an unrestricted pattern of expression of luminal and basal lineage markers. Consistent with this, SPADE analysis revealed that immature lobules were enriched for basal progenitor cells, while mature lobules consisted of increased hierarchal complexity of cells within the luminal lineages. These results reveal underlying differences in the human breast epithelial hierarchy and suggest that with increasing glandular maturity, the epithelial hierarchy also becomes more complex. The online version of this article (doi:10.1186/s13058-014-0453-3) contains supplementary material, which is available to authorized users.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
3.8
作者：
RUSSO, J;RIVERA, R;RUSSO, IH
通讯作者：
RUSSO, IH
DOI：
10.1073/pnas.0401064101
发表时间：
2004-04-06
影响因子：
11.1
作者：
Kuperwasser, C;Chavarria, T;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
2.9
作者：
OHARE, MJ;ORMEROD, MG;GUSTERSON, BA
通讯作者：
GUSTERSON, BA
影响因子：
82.9
作者：
Ceradini, DJ;Kulkarni, AR;Gurtner, GC
通讯作者：
Gurtner, GC