Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling

	Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling
	Yang, X; Xu, HB; Yang, X; Wang, H; Zou, L; Yang, Q; Qi, XP; Li, L; Duan, HX; Yan, XY; Fu, NY; Tan, J; Hou, ZL; Jiao, BW
	2024
发表期刊	NATURE COMMUNICATIONS
卷号	15 期号:1
摘要	While canonical Wnt signaling is well recognized for its crucial regulatory functions in cell fate decisions, the role of non-canonical Wnt signaling in adult stem cells remains elusive and contradictory. Here, we identified Mcam, a potential member of the non-canonical Wnt signaling, as an important negative regulator of mammary gland epithelial cells (MECs) by genome-scale CRISPR-Cas9 knockout (GeCKO) library screening. Loss of Mcam increases the clonogenicity and regenerative capacity of MECs, and promotes the proliferation, differentiation, and ductal morphogenesis of mammary epithelial in knockout mice. Mechanically, Mcam knockout recruits and polarizes macrophages through the Il4-Stat6 axis, thereby promoting secretion of the non-canonical Wnt ligand Wnt5a and its binding to the non-canonical Wnt signaling receptor Ryk to induce the above phenotypes. These findings reveal Mcam roles in mammary gland development by orchestrating communications between MECs and macrophages via a Wnt5a/Ryk axis, providing evidences for non-canonical Wnt signaling in mammary development. Mammary epithelial cells act to continuously renew the mammary tissue and must balance differentiation and self-renewal. Here they show that Mcam, a non-canonical Wnt pathway member, regulates communication between macrophages and mammary epithelial cells, thereby maintaining self-renewal and subsequently promoting mammary ductal morphogenesis.
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/152453/14262
专题	科研部门_发育的印迹调控与进化学（焦保卫）
推荐引用方式 GB/T 7714	Yang, X,Xu, HB,Yang, X,et al. Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling[J]. NATURE COMMUNICATIONS,2024,15(1).
APA	Yang, X.,Xu, HB.,Yang, X.,Wang, H.,Zou, L.,...&Jiao, BW.(2024).Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling.NATURE COMMUNICATIONS,15(1).
MLA	Yang, X,et al."Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling".NATURE COMMUNICATIONS 15.1(2024).

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