Project description:The mammary epithelia are mainly composed of two distinct lineages, the basal and luminal cells. In our MMTV-Cre; Brca1flox/flox mouse model, we found the Brca1 knockout mainly occurred in the luminal cells, which will lead the mammary tumorigenesis. To investigate the Brca1 deficiency mediated mammary tumorigenesis, we sorted the luminal cells from wild type mice and MMTV-Cre; Brca1flox/flox mice for RNAseq analysis.
Project description:We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all. We performed an expression analysis on luminal mammary epithelial cells sorted based on their Venus expression (reporting Tbx3 promoter activity) to investigate the difference between these two cell populations. Mammary epithelial cells from 3 Tbx3-Venus-KI adult virgin female mice (FVB background) were pooled and luminal cells were sorted into a Venus-hi and a Venus-neg sample. There were no repeats for this study.
Project description:We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all. We performed an expression analysis on luminal mammary epithelial cells sorted based on their Venus expression (reporting Tbx3 promoter activity) to investigate the difference between these two cell populations.
Project description:The mammary luminal cell compartment is heterogeneous. In adult virgin mice, it contains clonogenic luminal progenitors and non-clonogenic luminal cells expressing estrogen and progesterone receptors that can be discrimated by their cell surface expression of ICAM-1. We have separated ICAM1+ luminal progenitors and ICAM- non-clonogenic luminal cells and analyzed their transcriptomic profiles. After showing that the luminal progenitor population overexpressed Met, Trp53 and numerous p53 target genes, we analyzed how the p53 and Met signaling pathways cooperate to control the function and plasticity of luminal progenitors.
Project description:Mammary gland homeostasis is maintained by adult tissue stem-progenitor cells residing within the luminal and basal epithelia. Dysregulation of mammary stem cells is a key mechanism for cancer development. However, stem cell characterization is challenging because reporter models using cell-specific promoters do not fully recapitulate the mammary stem cell populations. We previously found that a 270-basepair Runx1 enhancer element, named eR1, marked stem cells in the blood and stomach. Here, we identified eR1 activity in a rare subpopulation of the ERα-negative luminal epithelium in mouse mammary glands. Lineage-tracing using an eR1-CreERT2 mouse model revealed that eR1+ luminal cells generated the entire luminal lineage and milk-secreting alveoli – eR1 therefore specifically marks lineage-restricted luminal stem cells. eR1-targeted-conditional knockout of Runx1 led to the expansion of luminal epithelial cells, accompanied by elevated ERα expression. Our findings demonstrate a definitive role for Runx1 in the regulation of the eR1-positive luminal stem cell proliferation during mammary homeostasis. Our findings identify a mechanistic link for Runx1 in stem cell proliferation and its dysregulation in breast cancer. Runx1 inactivation is therefore likely to be an early hit in the cell-of-origin of ERα+ luminal type breast cancer.
Project description:The aim of this project is to examine age-dependent changes in the proteomes and phosphoproteomes of normal human mammary luminal epithelial and myoepithelial cells.
Project description:Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we provide evidence that the protein kinase p38a is required for the differentiation of luminal progenitor cells through modulation of the transcription factors Runx1 and Foxa1. Moreover, using a mouse model for breast cancer initiated by luminal cells, we show that p38a downregulation in mammary epithelial cells reduces tumorigenesis, which correlates with reduced numbers of tumor-initiating cells. Our results identify p38a as a key regulator of luminal progenitor cell fate that facilitates mammary tumor formation.
Project description:We report here the transcriptional signature of Notch1-expressing (GFP positive) luminal mammary progenitors compared to total luminal cells (GFP negative). For each condition, 3 biological replicates were performed, by pooling the mammary glands from two mice/replicate.
Project description:MaSC and luminal enriched subpopulations were sorted based on CD24/CD29 expression from mammary epithelial cells of virgin female mice . (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035), and the microRNA profiles were determined using microRNA array and compared.