Differential Gene Expression in Nuclear Label-Retaining Cells in the Developing Mouse Mammary Gland

Park, Jang Pyo; Raafat, Ahmed; Feltracco, Jessica A.; Blanding, Walker M.; Booth, Brian W.

doi:10.1089/scd.2012.0496

Cited by 8 publications

(19 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The two-week labeling protocol in each of these studies encompassed a much longer period of ductal elongation than in our experiments and may have widened the distribution of LLRCs. In addition to confirming these previous studies [ 20 ],[ 22 ],[ 39 ], we have identified an embryonically derived stem/progenitor cell population that is activated both during puberty and pregnancy. A small number of the eLLRCs that also incorporate BrdU persist as long-term double-labeled cells.…”

Section: Discussionsupporting

confidence: 89%

“…A small number of the eLLRCs that also incorporate BrdU persist as long-term double-labeled cells. However, whether these double-labeled cells represent the same population as the previously reported adult LLRCs remains unknown [ 20 ],[ 22 ],[ 39 ]. Future gene expression profiling of double-labeled EdU + BrdU + eLLRCs may shed light on this question and could enable the identification of more precise markers for quiescent stem cells.…”

Section: Discussionmentioning

confidence: 94%

“…Our results suggest that LLRCs labeled during puberty are generally located in the middle of the gland and we did not find these cells at the leading edges of the ducts. Previous studies also labeled during puberty but only one mentioned a specific distribution pattern of label-retaining cells [ 20 ],[ 22 ],[ 39 ]. Multi-scale in-situ analysis revealed that the ventral-most, large ducts near the nipple region contained a reservoir of undifferentiated, putative stem cells similar to our studies, although the LLRCs were not restricted to this region in their study [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland

2014

View full text Add to dashboard Cite

IntroductionStudies have identified multi-potent stem cells in the adult mammary gland. More recent studies have suggested that the embryonic mammary gland may also contain stem/progenitor cells that contribute to initial ductal development. We were interested in determining whether embryonic cells might also directly contribute to long-lived stem cells that support homeostasis and development in the adult mammary gland.MethodsWe used DNA-label retention to detect long label-retaining cells in the mammary gland. Mouse embryos were labeled with 5-ethynl-2′-deoxyuridine (EdU) between embryonic day 14.5 and embryonic day 18.5 and were subsequently sacrificed and examined for EdU retention at various intervals after birth. EdU retaining cells were co-stained for various lineage markers and identified after fluorescence activated cell sorting analysis of specific epithelial subsets. EdU-labeled mice were subjected to subsequent 5-bromo-2′-deoxyuridine administration to determine whether EdU-labeled cells could re-enter the cell cycle. Finally, EdU-labeled cells were grown under non-adherent conditions to assess their ability to form mammospheres.ResultsWe demonstrate embryonically-derived, long label-retaining cells (eLLRCs) in the adult mammary gland. eLLRCs stain for basal markers and are enriched within the mammary stem cell population identified by cell sorting. eLLRCs are restricted to the primary ducts near the nipple region. Interestingly, long label retaining cells (labeled during puberty) are found just in front of the eLLRCs, near where the ends of the ducts had been at the time of DNA labeling in early puberty. A subset of eLLRCs becomes mitotically active during periods of mammary growth and in response to ovarian hormones. Finally, we show that eLLRCs are contained within primary and secondary mammospheres.ConclusionsOur findings suggest that a subset of proliferating embryonic cells subsequently becomes quiescent and contributes to the pool of long-lived mammary stem cells in the adult. eLLRCs can re-enter the cell cycle, produce both mammary lineages and self-renew. Thus, our studies have identified a putative stem/progenitor cell population of embryonic origin. Further study of these cells will contribute to an understanding of how quiescent stem cells are generated during development and how fetal exposures may alter future breast cancer risk in adults.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0487-6) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland

2014

View full text Add to dashboard Cite

show abstract

“…Activation of Notch1 results in an expansion of mammary luminal progenitor cells [ 28 ]. Notch1 and Notch2 regulate asymmetric division of mammary progenitor cells during pubertal development [ 29 ]. Inhibition of Notch1 reduces cancer stem cell function, reduces expression of Notch target genes HES1 , HES5 and HEY-L , and reduces the population of CD44 Hi CD24 low , a population identified as cancer stem cells [ 30 – 32 ].…”

Section: Discussionmentioning

confidence: 99%

Cancer cell redirection biomarker discovery using a mutual information approach

et al. 2017

Self Cite

View full text Add to dashboard Cite

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection biomarkers that cause the redirected state to shift toward the normal expression pattern, we used mutual information relationships between normal, redirected, and tumor cell groups. Mutual information relationship analysis reduced a dataset of over 35,000 gene expression measurements spread over 13,000 curated gene sets to a set of 20 significant molecular signatures totaling 906 unique loci. Several of these molecular signatures are hallmark drivers of the tumor state. Using differential expression as a guide, we further refined the gene set to 120 core redirection biomarker genes. The expression levels of these core biomarkers are sufficient to make the normal and redirected gene expression states indistinguishable from each other but radically different from the tumor state.

show abstract

“…Notch serves as a regulator for decisions related to asymmetric fate of cells [ 51 ]. Notch1 and Notch2 have been found localized in the nuclei of prospective mammary progenitor cells [ 85 ]. Under the regulation of the mouse mammary tumor virus promoter, transgenic mice with a constitutively active Notch4 exhibited suspended mammalian gland growth and ultimately developed poorly differentiated adenocarcinoma [ 84 ].…”

Section: Stem Cells Of the Mammary Glandmentioning

confidence: 99%

Asymmetric cell division of mammary stem cells

Chhabra

Booth

2021

Cell Div

Self Cite

View full text Add to dashboard Cite

Somatic stem cells are distinguished by their capacity to regenerate themselves and also to produce daughter cells that will differentiate. Self-renewal is achieved through the process of asymmetric cell division which helps to sustain tissue morphogenesis as well as maintain homeostasis. Asymmetric cell division results in the development of two daughter cells with different fates after a single mitosis. Only one daughter cell maintains “stemness” while the other differentiates and achieves a non-stem cell fate. Stem cells also have the capacity to undergo symmetric division of cells that results in the development of two daughter cells which are identical. Symmetric division results in the expansion of the stem cell population. Imbalances and deregulations in these processes can result in diseases such as cancer. Adult mammary stem cells (MaSCs) are a group of cells that play a critical role in the expansion of the mammary gland during puberty and any subsequent pregnancies. Furthermore, given the relatively long lifespans and their capability to undergo self-renewal, adult stem cells have been suggested as ideal candidates for transformation events that lead to the development of cancer. With the possibility that MaSCs can act as the source cells for distinct breast cancer types; understanding their regulation is an important field of research. In this review, we discuss asymmetric cell division in breast/mammary stem cells and implications on further research. We focus on the background history of asymmetric cell division, asymmetric cell division monitoring techniques, identified molecular mechanisms of asymmetric stem cell division, and the role asymmetric cell division may play in breast cancer.

show abstract

Differential Gene Expression in Nuclear Label-Retaining Cells in the Developing Mouse Mammary Gland

Cited by 8 publications

References 58 publications

Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland

Embryonic cells contribute directly to the quiescent stem cell population in the adult mouse mammary gland

Cancer cell redirection biomarker discovery using a mutual information approach

Asymmetric cell division of mammary stem cells

Contact Info

Product

Resources

About