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Title: A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells
Authors: Matsuo, Junichi 
Mon, Naing Naing 
Douchi, Daisuke
Yamamura, Akihiro 
Kulkarni, Madhura 
Heng, Dede Liana
Chen, Sabirah 
Nuttonmanit, Napat 
Li, Ying 
Yang, Henry 
Lee, May Yin
Tam, Wai Leong 
Osato, Motomi 
Chuang, Linda Shyue Huey 
Ito, Yoshiaki 
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell & Tissue Engineering
Biotechnology & Applied Microbiology
Cell Biology
mammary gland
stem cell
ER alpha
Issue Date: 3-Mar-2022
Citation: Matsuo, Junichi, Mon, Naing Naing, Douchi, Daisuke, Yamamura, Akihiro, Kulkarni, Madhura, Heng, Dede Liana, Chen, Sabirah, Nuttonmanit, Napat, Li, Ying, Yang, Henry, Lee, May Yin, Tam, Wai Leong, Osato, Motomi, Chuang, Linda Shyue Huey, Ito, Yoshiaki (2022-03-03). A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells. STEM CELLS 40 (1) : 112-122. ScholarBank@NUS Repository.
Abstract: Abstract 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.
Source Title: STEM CELLS
ISSN: 1066-5099
DOI: 10.1093/stmcls/sxab009
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