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Frontiers in Biology

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CN 11-5892/Q

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Front. Biol.    2014, Vol. 9 Issue (3) : 175-185    https://doi.org/10.1007/s11515-014-1308-0
REVIEW
The dynamics of murine mammary stem/progenitor cells
Qiaoxiang DONG1,2,*(),Lu-Zhe SUN1,3,*()
1. Department of Cellular & Structural Biology, University of Texas Health Science Center, San Antonio, TX 78299, USA
2. Institute of Environmental Safety and Human Health, Wenzhou Medical University, University Town, Wenzhou 325035, China
3. Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX 78299, USA
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Abstract

The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups.
Keywords mammary stem cell      cell hierarchy     
Corresponding Author(s): Qiaoxiang DONG   
Issue Date: 24 June 2014
 Cite this article:   
Qiaoxiang DONG,Lu-Zhe SUN. The dynamics of murine mammary stem/progenitor cells[J]. Front. Biol., 2014, 9(3): 175-185.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-014-1308-0
https://academic.hep.com.cn/fib/EN/Y2014/V9/I3/175
Model systemStem or progenitorsNicheLineage specification?MRU ?frequencyReference
in vivo labelingTransplant
WC/R26-lacZPI-MECCD24+CD49fhiAlveolar terminal ductsBasal*Bipotent?–Wagner et al., 2002Matulka et al., 2007
Tg11.5kb-GFPs-SHIP+Cap cellsAlveolar budsBasalBasalBipotentBipotent?1/48?1/79Bai and Rohrschneider, 2010
Axin2CreERT2Axin2+Fetal budPre-pubertal basalPubertal TEBsAdult basalAdult basalLuminalBasalBasal or luminalBasal (virgin)Bipotent (preg)–Bipotent–Bipotent–?–van Amerongen et al., 2012
Lgr5–EGFP–Ires–CreERT2Lgr5+PND1PND12LuminalBasal–Bipotent?–?1/1781de Visser et al., 2012
Lgr5-EGFPLgr5+Nipple areaBasalBipotent?1/3.7Plaks et a. 2013
K5tTA/H2B-GFPCD24+CD49fhiGFP+CD61-Tips of TEBBasalBipotent?1/33dos Santos et al., 2013
MMTVrtTA/H2B-GFPCD24+CD29loGFP+Luminal layerLuminal*Bipotent?1/350Kaanta et al., 2013
Tab.1  Stem/progenitors within the murine mammary gland identified by different model systems
Fig.1  (A) Regenerated glands in virgin mice by GFP positive MaSCs showing non-epithelial cells (black) in the luminal (CD24hiCD49f+) or basal (CD24+CD49fhi) gates together with epithelial cells (green). Right panels show the histograms of %GFP negative (stromal) and positive (epithelial) cells in each gate. (B) Morphological distinct 3D-ECM organoids derived from single spheres formed by FACS sorted luminal (CD24hiCD49flo) cells from C57BL6 mice aged 3 to 4 months. Scale bars, 100 µm. (Reprinted from Dong et al., Mammospheres from murine mammary stem cell-enriched basal cells: clonal characteristics and repopulating potential. Stem Cell Research, 2013 (10): 396-404 with permission from Elsevier.)
Fig.2  Schematic model of the murine mammary epithelial hierarchy: bipotent stem cells in fetus give rise to luminal (filled in red color) and basal (filled in gray color) progenitors in prepubertal and pubertal glands. The luminal and basal lineage can be further divided into ductal (shaped with black outline) and alveolar-restricted (shaped with purple outline) progenitors. The luminal and basal alveolar progenitors are to be activated during pregnancy. The triangle bar indicates progenitor cells with decreasing multi- or uni-potency during the development from prepubertal to adult glands. Curves represent different stem/progenitors that are predominant in the epithelial cell population at different developmental stages. The dashed lines indicate potential possibilities. Cell markers labeled under each stem/progenitor cells correspond to published studies (see Text for details).
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