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Title: Gene expression analysis of FACS-isolated mammary stromal cells (Fsp1-expressing) between stromal Gli2 wild type control and stromal Gli2 ablated mice      
keywords:
Transcriptome or Gene expression
ID:
PRJNA278039
description:
The capacity of stem cells to maintain and regenerate organs is critically dependent on the niche, a complex signaling microenvironment that sustains and regulates stem cell activity. Niche function in the mammary gland must integrate local homeostatic activities with hormonally regulated events, such as pregnancy or the onset of puberty. In the human disorder CPHD (combined pituitary hormone deficiency) breast growth defects at puberty are associated with mutations disrupting the transcription factor, GLI2. Here we find that Gli2 functions in mouse mammary stromal cells to shape a niche signaling program that sustains mammary epithelial stem cells. Ablation of Gli2 in stromal cells thus leads to a disorganized mammary gland, associated with collapse of the niche signaling environment, with a five-fold decrease in functional mammary stem cell activity, and with attenuated response to the mammatrophic hormones estrogen and growth hormone. Consistent with a niche defect, aspects of Gli2-deficient mammary gland architecture can be rescued by local supplementation with IGF and WNT protein signals. Our findings thus identify GLI2 as a critical coordinator of local and hormonal influences on the niche signaling program, and suggest that mammary pathogenesis in CPHD patients results from dysfunction of the mammary epithelial stem cell niche. We used microarrays to identify gene expression signatures associated with stromal Gli2 expression Overall design: To identify stromal factors induced by Gli2 activity, we compared gene expression of FACS-isolated Fsp1Cre-marked stromal cells from Gli2∆S or Gli2WT littermates by microarray analysis, and identified genes encoding paracrine factors such as Igf1, Wnt2, Hgf, Fgf7, and Bmp7; we also identified down-regulated genes encoding estrogen receptor (Esr1), growth hormone receptor (Ghr), and other genes typically expressed in stromal cells. Of particular interest among the paracrine factors, WNT signals sustain the activity of MaSCs and in ex vivo culture, and functional inactivation of Igf1 or its epithelially expressed receptor, Igf-1r, both lead to development of hypoplastic mammary glands with terminal end bud abnormalities similar to the defects we observe in Gli2∆S mice. The down-regulation of these genes was confirmed by qRT-PCR of bulk stromal cells from Gli2WT and Gli2∆S mice, and was further quantified by qRT-PCR from single cells
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA278039
authentication:
none
authorization:
none
name:
Mus musculus
ncbiID:
ncbitax:10090
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject