دورية أكاديمية
A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells.
| العنوان: | A Runx1-enhancer Element eR1 Identified Lineage Restricted Mammary Luminal Stem Cells. |
|---|---|
| المؤلفون: | Matsuo J; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Mon NN; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Douchi D; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Yamamura A; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan., Kulkarni M; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Center for Translational Cancer Research - a joint initiative between Prashanti Cancer Care Mission and Indian Institute of Science Education and Research, Pune, Maharashtra, India., Heng DL; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Chen S; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Nuttonmanit N; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Li Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Lee MY; Genome Institute of Singapore, A∗STAR, Singapore, Singapore., Tam WL; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Genome Institute of Singapore, A∗STAR, Singapore, Singapore., Osato M; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Chuang LSH; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore., Ito Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. |
| المصدر: | Stem cells (Dayton, Ohio) [Stem Cells] 2022 Mar 03; Vol. 40 (1), pp. 112-122. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 9304532 Publication Model: Print Cited Medium: Internet ISSN: 1549-4918 (Electronic) Linking ISSN: 10665099 NLM ISO Abbreviation: Stem Cells Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2022- : Oxford : Oxford University Press Original Publication: Dayton, OH : AlphaMed Press, c1993- |
| مواضيع طبية MeSH: | Estrogen Receptor alpha*/genetics , Estrogen Receptor alpha*/metabolism , Mammary Glands, Animal*, Animals ; Cell Lineage ; Core Binding Factor Alpha 2 Subunit/genetics ; Core Binding Factor Alpha 2 Subunit/metabolism ; Enhancer Elements, Genetic/genetics ; Epithelial Cells/metabolism ; Mice ; Stem Cells/metabolism |
| مستخلص: | 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. (© The Author(s) 2022. Published by Oxford University Press.) |
| فهرسة مساهمة: | Keywords: ERα; Runx1; eR1; enhancer; mammary gland; stem cell |
| المشرفين على المادة: | 0 (Core Binding Factor Alpha 2 Subunit) 0 (Estrogen Receptor alpha) 0 (Runx1 protein, mouse) |
| تواريخ الأحداث: | Date Created: 20220505 Date Completed: 20220509 Latest Revision: 20220531 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1093/stmcls/sxab009 |
| PMID: | 35511868 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1549-4918 |
|---|---|
| DOI: | 10.1093/stmcls/sxab009 |