Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland

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	Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland
	Wang, ZB; Zhang, L; Li, B; Song, JG; Yu, M; Zhang, J; Chen, CS; Zhan, J; Zhang, HQ
	2023
发表期刊	CELL DEATH & DISEASE
ISSN	2041-4889
卷号	14 期号:10
摘要	Myoepithelium plays an important role in mammary gland development, but less is known about the molecular mechanism underlying how myoepithelium controls acinus differentiation during gestation. Herein, we found that loss of Kindlin-2 in myoepithelial cells impaired mammary morphogenesis, alveologenesis, and lactation. Using five genetically modified mouse lines combined with single-cell RNA sequencing, we found a Kindlin-2-Stat3-Dll1 signaling cascade in myoepithelial cells that inactivates Notch signaling in luminal cells and consequently drives luminal progenitor commitment to alveolar cells identity. Single-cell profiling revealed that Kindlin-2 loss significantly reduces the proportion of matured alveolar cells. Mechanistically, Kindlin-2 depletion in myoepithelial cells promotes Stat3 activation and upregulates Dll1, which activates the Notch pathway in luminal cells and inhibits luminal progenitor differentiation and maturation during gestation. Inhibition of Notch1 with tangeretin allowed luminal progenitors to regain commitment ability in the pregnant mice with Kindlin-2 depletion in myoepithelium. Taken together, we demonstrated that Kindlin-2 is essential to myoepithelium-controlled luminal progenitors to alveoli transition during gestation.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14186
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Wang, ZB,Zhang, L,Li, B,et al. Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland[J]. CELL DEATH & DISEASE,2023,14(10).
APA	Wang, ZB.,Zhang, L.,Li, B.,Song, JG.,Yu, M.,...&Zhang, HQ.(2023).Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland.CELL DEATH & DISEASE,14(10).
MLA	Wang, ZB,et al."Kindlin-2 in myoepithelium controls luminal progenitor commitment to alveoli in mouse mammary gland".CELL DEATH & DISEASE 14.10(2023).

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