FGD5 in basal cells induces CXCL14 secretion that initiates a feedback loop to promote murine mammary epithelial growth and differentiation

被引:4
作者
Zhang, Tingting [1 ]
Zhao, Chenxi [1 ]
Li, Yunxuan [1 ]
Wu, Jie [1 ]
Wang, Feng [1 ]
Yu, Jinmei [2 ]
Wang, Zhenhe [2 ]
Gao, Yang [1 ]
Zhao, Luyao [1 ]
Liu, Ying [1 ]
Yan, Yechao [1 ]
Li, Xia [3 ]
Gao, Huan [3 ]
Hu, Zhuowei [2 ]
Cui, Bing [2 ]
Li, Ke [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, NHC Key Lab Biotechnol Antibiot, Beijing 100050, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, CAMS Key Lab Mol Mech & Target Discovery Metab Dis, Beijing 100050, Peoples R China
[3] Shandong Univ, Marine Coll, Weihai 264200, Peoples R China
基金
国家重点研发计划;
关键词
STEM-CELL; GLAND DEVELOPMENT; MESENCHYMAL TRANSITION; MULTIPOTENCY; METASTASIS; TRANSDUCER; HIERARCHY; SURVIVAL; HYPOXIA; TISSUE;
D O I
10.1016/j.devcel.2024.05.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland. Conditional deletion of Fgd5 reduced, whereas conditional knockin of Fgd5 increased, the engraftment and expansion of BCs, regulating ductal morphogenesis in the mammary gland. Mechanistically, murine mammary BC-expressed FGD5 inhibited the transcriptional activity of activating transcription factor 3 (ATF3), leading to subsequent transcriptional activation and secretion of CXCL14. Furthermore, activation of CXCL14/CXCR4/ERK signaling in primary murine mammary stromal ECs enhanced the expression of HIF-1cc-regulated hedgehog ligands, which initiated a positive feedback loop to promote the function of BCs. Collectively, these findings identify functionally important interactions between BCs and the endothelial niche that occur through the FGD5/CXCL14/hedgehog axis.
引用
收藏
页码:2085 / 2100.e9
页数:26
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