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乳腺中多能干细胞的原位鉴定。

In situ identification of bipotent stem cells in the mammary gland.

机构信息

1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia [3].

1] Stem Cells and Cancer Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia [2] Department of Medicine, The University of Melbourne, Parkville, Victoria 3010, Australia [3] Department of Medical Oncology and Familial Cancer Centre, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.

出版信息

Nature. 2014 Feb 20;506(7488):322-7. doi: 10.1038/nature12948. Epub 2014 Jan 26.

DOI:10.1038/nature12948
PMID:24463516
Abstract

The mammary epithelium undergoes profound morphogenetic changes during development. Architecturally, it comprises two primary lineages, the inner luminal and outer myoepithelial cell layers. Two opposing concepts on the nature of mammary stem cells (MaSCs) in the postnatal gland have emerged. One model, based on classical transplantation assays, postulates that bipotent MaSCs have a key role in coordinating ductal epithelial expansion and maintenance in the adult gland, whereas the second model proposes that only unipotent MaSCs identified by lineage tracing contribute to these processes. Through clonal cell-fate mapping studies using a stochastic multicolour cre reporter combined with a new three-dimensional imaging strategy, we provide evidence for the existence of bipotent MaSCs as well as distinct long-lived progenitor cells. The cellular dynamics at different developmental stages support a model in which both stem and progenitor cells drive morphogenesis during puberty, whereas bipotent MaSCs coordinate ductal homeostasis and remodelling of the mouse adult gland.

摘要

在发育过程中,乳腺上皮经历了深刻的形态发生变化。从结构上看,它由两个主要谱系组成,即内腔腔和外肌上皮细胞层。关于产后乳腺干细胞(MaSCs)性质的两种对立概念已经出现。一种基于经典移植测定的模型假设,双能 MaSCs 在协调成年腺体中的导管上皮扩张和维持中起关键作用,而第二种模型则提出,只有通过谱系追踪鉴定的单能 MaSCs 才能促进这些过程。通过使用随机多色 cre 报告基因与新的三维成像策略进行克隆细胞命运映射研究,我们为双能 MaSCs 以及不同的长寿祖细胞的存在提供了证据。不同发育阶段的细胞动力学支持这样一种模型,即干细胞和祖细胞都在青春期驱动形态发生,而双能 MaSCs 则协调导管的稳态和成年小鼠腺体的重塑。

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In situ identification of bipotent stem cells in the mammary gland.乳腺中多能干细胞的原位鉴定。
Nature. 2014 Feb 20;506(7488):322-7. doi: 10.1038/nature12948. Epub 2014 Jan 26.
2
Mammary stem cells and the differentiation hierarchy: current status and perspectives.乳腺干细胞及其分化层次:现状与展望。
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J Mammary Gland Biol Neoplasia. 2025 Jul 17;30(1):11. doi: 10.1007/s10911-025-09586-4.
2
Intraductal Injection of Adenoviruses to Perform Lineage Tracing in the Mammary Gland.通过导管内注射腺病毒在乳腺中进行谱系追踪。
J Mammary Gland Biol Neoplasia. 2025 Jul 7;30(1):10. doi: 10.1007/s10911-025-09584-6.
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CXCR4 mammary gland macrophageal niche promotes tumor initiating cell activity and immune suppression during tumorigenesis.

本文引用的文献

1
Molecular hierarchy of mammary differentiation yields refined markers of mammary stem cells.乳腺分化的分子层次结构产生了乳腺干细胞的精细标志物。
Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7123-30. doi: 10.1073/pnas.1303919110. Epub 2013 Apr 11.
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Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis.Lgr5 表达细胞对于出生后乳腺器官发生是充分和必要的。
Cell Rep. 2013 Jan 31;3(1):70-8. doi: 10.1016/j.celrep.2012.12.017. Epub 2013 Jan 24.
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Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland.
CXCR4乳腺巨噬细胞生态位在肿瘤发生过程中促进肿瘤起始细胞活性和免疫抑制。
Nat Commun. 2025 May 25;16(1):4854. doi: 10.1038/s41467-025-59972-z.
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Distinct mammary stem cells orchestrate long-term homeostasis of adult mammary gland.不同的乳腺干细胞协调成年乳腺的长期稳态。
Cell Discov. 2025 Apr 15;11(1):39. doi: 10.1038/s41421-025-00794-0.
5
Noncanonical Wnt/Ror2 Signaling Regulates Basal Cell Fidelity and Branching Morphogenesis in the Mammary Gland.非经典Wnt/Ror2信号通路调控乳腺中的基底细胞保真度和分支形态发生。
bioRxiv. 2025 Feb 25:2025.02.25.640099. doi: 10.1101/2025.02.25.640099.
6
Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.实体瘤癌症干细胞中膳食化合物的分子机制:对结直肠癌、乳腺癌和前列腺癌的见解
Int J Mol Sci. 2025 Jan 13;26(2):631. doi: 10.3390/ijms26020631.
7
Cells-of-Origin of Breast Cancer and Intertumoral Heterogeneity.乳腺癌的起源细胞与肿瘤间异质性
Adv Exp Med Biol. 2025;1464:151-165. doi: 10.1007/978-3-031-70875-6_9.
8
Breast Morphogenesis: From Normal Development to Cancer.乳腺形态发生:从正常发育到癌症
Adv Exp Med Biol. 2025;1464:29-44. doi: 10.1007/978-3-031-70875-6_3.
9
Oncogene activated human breast luminal progenitors contribute basally located myoepithelial cells.致癌基因激活的人乳腺腔面祖细胞可产生位于基底的肌上皮细胞。
Breast Cancer Res. 2024 Dec 18;26(1):183. doi: 10.1186/s13058-024-01939-x.
10
Luminal breast epithelial cells of BRCA1 or BRCA2 mutation carriers and noncarriers harbor common breast cancer copy number alterations.携带BRCA1或BRCA2基因突变者与非携带者的管腔型乳腺上皮细胞存在常见的乳腺癌拷贝数改变。
Nat Genet. 2024 Dec;56(12):2753-2762. doi: 10.1038/s41588-024-01988-0. Epub 2024 Nov 20.
乳腺管腔细胞层级的表型和功能特征
Breast Cancer Res. 2012 Oct 22;14(5):R134. doi: 10.1186/bcr3334.
4
Distinct contribution of stem and progenitor cells to epidermal maintenance.干细胞和祖细胞对表皮维持的独特贡献。
Nature. 2012 Sep 13;489(7415):257-62. doi: 10.1038/nature11393.
5
Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland.LGR5(+) 细胞在出生后乳腺中基底和腔上皮谱系的发育阶段特异性贡献。
J Pathol. 2012 Nov;228(3):300-9. doi: 10.1002/path.4096.
6
Developmental stage and time dictate the fate of Wnt/β-catenin-responsive stem cells in the mammary gland.发育阶段和时间决定了乳腺中 Wnt/β-连环蛋白反应性干细胞的命运。
Cell Stem Cell. 2012 Sep 7;11(3):387-400. doi: 10.1016/j.stem.2012.05.023. Epub 2012 Aug 2.
7
The proto-oncogene Myc is essential for mammary stem cell function.原癌基因 Myc 对于乳腺干细胞功能至关重要。
Stem Cells. 2012 Jun;30(6):1246-54. doi: 10.1002/stem.1090.
8
Lineage tracing.谱系追踪。
Cell. 2012 Jan 20;148(1-2):33-45. doi: 10.1016/j.cell.2012.01.002.
9
Distinct stem cells contribute to mammary gland development and maintenance.不同的干细胞对乳腺的发育和维持起着重要作用。
Nature. 2011 Oct 9;479(7372):189-93. doi: 10.1038/nature10573.
10
Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip.胚层和谱系限制的干细胞/祖细胞可使小鼠指尖再生。
Nature. 2011 Aug 24;476(7361):409-13. doi: 10.1038/nature10346.