Identification of Stem Cell Units in the Terminal End Bud and Duct of the Mouse Mammary Gland

Kenney, Nicholas; Smith, Gilbert H.; Lawrence, Erin M; Barrett, J. Carl; Salomon, David

doi:10.1155/s1110724301000304

Cited by 86 publications

(69 citation statements)

References 34 publications

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“…Injury-responsive stem cells and their niches have been described in a variety of tissues, such as skin and hair follicle (6,8,9), mammary gland (10,11), and intestine (6,12). In some tissues, slow-cycling somatic stem cells were initially identified by their ability to retain label for long periods of time, whereas asymmetrically derived lineage committed daughter cells dilute out label during rapid proliferation and terminal differentiation (9,(13)(14)(15)(16)(17)(18). These studies, as well as the recent identification of label-retaining cells (LRCs) in the uterine endometrial stroma and myometrium (19), used BrdU, 3H-Thymidine, or histone2B-green fluorescent protein (H2B-GFP) labeling to identify candidate somatic stem cells.…”

mentioning

confidence: 99%

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

Szotek

Chang

Brennand

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

119

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Ovulation induces cyclic rupture and regenerative repair of the ovarian coelomic epithelium. This process of repeated disruption and repair accompanied by complex remodeling typifies a somatic stem/progenitor cell-mediated process. Using BrdU incorporation and doxycycline inducible histone2B-green fluorescent protein pulse–chase techniques, we identify a label-retaining cell population in the coelomic epithelium of the adult mouse ovary as candidate somatic stem/progenitor cells. The identified population exhibits quiescence with asymmetric label retention, functional response to estrous cycling in vivo by proliferation, enhanced growth characteristics by in vitro colony formation, and cytoprotective mechanisms by enrichment for the side population. Together, these characteristics identify the label-retaining cell population as a candidate for the putative somatic stem/progenitor cells of the coelomic epithelium of the mouse ovary.

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mentioning

confidence: 99%

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

Szotek

Chang

Brennand

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

119

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“…Sdc1À/À mammary glands are hypomorphic from embryogenesis through adulthood, with 50% fewer terminal end buds. Mammary end buds lead the extension of the developing ductal tree, and are widely considered to be the source of ductal stem cell activity (Kenney et al, 2001). Flow cytometric fractionation of dissociated cells from virgin adult Sdc1À/À ductal trees showed there were fewer cells in mammary progenitor-enriched fractions (Liu et al, 2004), and these glands showed a hypomorphic response to Wnt-induced stem cell amplification.…”

Section: Introductionmentioning

confidence: 99%

Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development

et al. 2006

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We previously showed that mice with a null mutation in syndecan-1 (Sdc1; CD138) were resistant to Wnt1-induced mammary tumor initiation. The absence of Sdc1 inhibited the increase in the mammary stem cell fraction that is characteristic of preneoplasia in this model. As the tumor precursor cells are recruited from the stem/ progenitor cell compartment, tumor development was also inhibited (Liu et al., 2004; PNAS 101, 4158). Although Sdc1À/À mice are grossly normal, they are systemically smaller, suggesting that developmental abnormalities may extend further than their mammary glands. We have therefore evaluated the multi-organ response of Sdc1À/À mice to carcinogen-induced tumor development (7,12-dimethylbenz[a]anthracene, DMBA), and find these mice to be resistant to tumorigenesis in all the predominant carcinogen-susceptible lineages. Thus, Sdc1À/À mice administered DMBA during juvenile development are resistant not only to epithelial tumors, including liver (60-80%) and lung tumors (C57BL6 mice, 60-80%), but also to lymphoma (over 70%, depending upon strain and carcinogen dose). We demonstrate that CD138 is expressed (heterogeneously) in the hematopoietic stem cell fraction (and not only in pre-B and plasma cells), and that tumors arise in both myeloid and lymphoid lineages. Furthermore, carcinogen-induced mammary tumors are bilineal, implying a bipotent precursor cell. Both observations imply that the DMBA-induced tumor precursor cells are drawn from the stem/progenitor fraction, and we suggest that pathogenic activation of these cells could be abnormal in Sdc1À/À mice.

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“…Within the murine mammary epithelia, a subset of SLC is thought to act as stem cells, whereas ULLC act as transit-amplifying cells, accounting for patches of these cells in rapidly proliferating mammary epithelium (during pregnancy and early lactation). Similar patches were also noted for label-retaining epithelial cells (LREC) and their progeny, which have been referred to as stem cell transitional units (Kenney et al, 2001).…”

Section: Identification Of Mascmentioning

confidence: 62%

Bovine mammary stem cells: cell biology meets production agriculture

Capuco

Choudhary

Daniels

et al. 2012

Animal

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Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue repair. Accordingly, we and others have attempted to characterize and alter the function of bovine MaSC. In this review, we provide an overview of current knowledge of MaSC gained from studies using mouse and human model systems and present research on bovine MaSC within that context. Recent data indicate that MaSC retain labeled DNA for extended periods because of their selective segregation of template DNA strands during mitosis. Relying on this long-term retention of bromodeoxyuridine-labeled DNA, we identified putative bovine MaSC. These label-retaining epithelial cells (LREC) are in low abundance within mammary epithelium (,1%). They are predominantly estrogen receptor (ER)-negative and localized in a basal or suprabasal layer of the epithelium throughout the gland. Thus, the response of MaSC to estrogen, the major mitogen in mammary gland, is likely mediated by paracrine factors released by cells that are ER-positive. This is consistent with considerable evidence for cross-talk within and between epithelial cells and surrounding stromal cells. Excision of classes of cells by laser microdissection and subsequent microarray analysis will hopefully provide markers for MaSC and insights into their regulation. Preliminary analyses of gene expression in laser-microdissected LREC and non-LREC are consistent with the concept that LREC represent populations of stem cells and progenitor cells that differ with regard to their properties and location within the epithelial layer. We have attempted to modulate the MaSC number by infusing a solution of xanthosine through the teat canal and into the ductal network of the mammary glands of prepubertal heifers. This treatment increased the number of putative stem cells, as evidenced by an increase in the percentage of LREC and increased telomerase activity within the tissue. The exciting possibility that stem cell expansion can influence milk production is currently under investigation.

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Identification of Stem Cell Units in the Terminal End Bud and Duct of the Mouse Mammary Gland

Cited by 86 publications

References 34 publications

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

Normal ovarian surface epithelial label-retaining cells exhibit stem/progenitor cell characteristics

Juvenile syndecan-1 null mice are protected from carcinogen-induced tumor development

Bovine mammary stem cells: cell biology meets production agriculture

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