High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units

Rauner, Gat; Kudinov, Tania; Gilad, Shlomit; Hornung, Gil; Barash, Itamar

doi:10.1016/j.stemcr.2018.05.013

Cited by 12 publications

(17 citation statements)

References 66 publications

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“…However, both CD200 high CD200R1 high MRUs and CD200 -CD200R1subset of MRUs shared some common stem cell markers. This suggested that CD200 high CD200R1 high MRUs represented stem cells, while CD200 -CD200R1 -MRUs represented common/bipotential progenitors [48]. Some CD200 high CD200R1 high cells did not show mammary regenerative activities and were though to represent more differentiated myoepithelial cells.…”

Section: Mouse Mammary Stem Cells and Progenitorsmentioning

confidence: 99%

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Bhat

Sun

Weger

et al. 2016

Stem Cells and Development

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The evolutionarily conserved Notch and Wnt signaling pathways have demonstrated roles in normal mammary gland development and in breast carcinogenesis. We previously reported that in human mammary gland, signaling through NOTCH3 alone regulates the commitment of the undifferentiated bipotential progenitors to the luminal cell fate, indicating that NOTCH3 may regulate the expression of unique genes apart from the other Notch receptors. In this study, we used gain of function and loss of function experiments and found that a Wnt signaling receptor, Frizzled7 (FZD7), is a unique and nonredundant target of NOTCH3 in human breast epithelial cells. Interestingly, neither the constitutively active forms of NOTCH1-2, 4 nor loss of expression of these receptors were able to alter expression of FZD7 in human breast epithelial cells. We further show that FZD7-expressing cells are found more frequently in the luminal progenitor-enriched subpopulation of cells obtained from breast reduction samples compared with the undifferentiated bipotent progenitors. Also, we show that NOTCH3-induced expression of FZD7 occurs in the absence of CSL (CBF1-Suppressor of Hairless-Lag-1). Our data suggest that noncanonical Notch signaling through NOTCH3 could modulate Wnt signaling via FZD7 and in this way, might be involved in luminal cell differentiation.

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Section: Mouse Mammary Stem Cells and Progenitorsmentioning

confidence: 99%

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Bhat

Sun

Weger

et al. 2016

Stem Cells and Development

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“…The SMART-Seq2 protocol (Picelli et al 2014) was adapted with several modifications, as described below, to generate libraries for bulk RNA-Seq of individual cell lines included in the HNSCC custom pool (see 'Cell line assignment') and for profiling of bronchial primary cells following senescence induction with etoposide ( fig. S4E) (Rauner et al, 2018). Between 100-200 cells were resuspended in lysis buffer containing Triton 0.2% and RNAase inhibitor, or pelleted, washed with PBS and resuspended in the lysis buffer.…”

Section: Bulk Rna-seq By Smart-seq2mentioning

confidence: 99%

Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity

Kinker

Greenwald

Tal

et al. 2019

Preprint

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Cultured cell lines are the workhorse of cancer research, but it is unclear to what extent they recapitulate the cellular heterogeneity observed among malignant cells in tumors, given the absence of a native tumor microenvironment. Here, we used multiplexed single cell RNA-seq to profile ~200 cancer cell lines. We uncovered expression programs that are recurrently heterogeneous within many cancer cell lines and are largely independent of observed genetic diversity. These programs of heterogeneity are associated with diverse biological processes, including cell cycle, senescence, stress and interferon responses, epithelial-to-mesenchymal transition, and protein maturation and degradation. Notably, some of these recurrent programs recapitulate those seen in human tumors, suggesting a prominent role of intrinsic plasticity in generating intra-tumoral heterogeneity. Moreover, the data allowed us to prioritize specific cell lines as model systems of cellular plasticity. We used two such models to demonstrate the dynamics, regulation and drug sensitivities associated with a cancer senescence program also observed in human tumors. Our work describes the landscape of cellular heterogeneity in diverse cancer cell lines, and identifies recurrent patterns of expression heterogeneity that are shared between tumors and specific cell lines and can thus be further explored in follow up studies.

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“…There is no individual marker that specifically identifies bovine mammary stem cells [ 10 , 11 ]. Nevertheless, a limited collection of genes that are highly expressed in mouse and human mammary stem cells has been analyzed in extracts of bovine mammary parenchyma [ 8 , 24 ]. All of these markers were highly expressed in the rapamycin-treated glands, by 8–20% more than in their vehicle-treated counterparts ( Fig 3B ).…”

Section: Resultsmentioning

confidence: 99%

“…Notable progress has been achieved in mouse mammary stem cell characterization since breakthrough studies were published, demonstrating reconstitution of a functional mammary gland by transplantation of a single or several stem cells into the de-epithelized mammary stroma [ 6 , 7 ]. Better separation from progenitors has been performed [ 8 ], new effectors, markers and subpopulations have been identified [Reviewed by [ 4 , 9 ]] and most importantly, unipotent luminal and basal stem cell populations with self-renewing potency have been identified in the postpartum mammary gland [ 1 ]. Together with their bipotent counterparts, these cells maintain the morphogenesis and homeostasis of the adult gland [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Intramammary rapamycin administration to calves induces epithelial stem cell self-renewal and latent cell proliferation and milk protein expression

Kosenko

Jacoby²,

Ross³

et al. 2022

PLoS ONE

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Mammary epithelial stem cells differentiate to create the basal and luminal layers of the gland. Inducing the number of differentiating bovine mammary stem cells may provide compensating populations for the milk-producing cells that die during lactation. Inhibition of mTOR activity by rapamycin signals self-renewal of intestinal stem cells, with similar consequences in the mouse mammary gland and in bovine mammary implants maintained in mice. The implementation of these results in farm animals for better mammary development and production was studied in 3-month-old calves. mTOR activity decreased by ~50% in mammary epithelial cells subjected to 3-week rapamycin administration, with no negative consequences on mammary morphology or β-casein expression. Subsequently, stem cell self-renewal was induced, reflected by a higher propagation rate of cultures from rapamycin-treated glands compared to respective controls and higher expression of selected markers. Followed by 4-day estrogen and progesterone administration, rapamycin significantly induced proliferation rate. Higher numbers of basal and luminal PCNA+ cells were detected in small ducts near the elongating sites as compared to large ducts, in which only luminal cells were affected. Rapamycin administration resulted in induction of individual milk protein genes’ expression, which was negatively correlated to their endogenous levels. The inductive effect of rapamycin on luminal cell number was confirmed in organoid cultures, but milk protein expression decreased, probably due to lack of oscillation in rapamycin levels. In conclusion, intramammary rapamycin administration is an effective methodology to reduce mTOR activity in bovine mammary epithelial cells and consequently, induce stem cell self-renewal. The latent positive effect of rapamycin on epithelial cell proliferation and its potential to improve milk protein expression in calves may have beneficial implications for mature cows.

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High Expression of CD200 and CD200R1 Distinguishes Stem and Progenitor Cell Populations within Mammary Repopulating Units

Cited by 12 publications

References 66 publications

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells

Pan-cancer single cell RNA-seq uncovers recurring programs of cellular heterogeneity

Intramammary rapamycin administration to calves induces epithelial stem cell self-renewal and latent cell proliferation and milk protein expression

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