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

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

  • Dev Cell. 2024 May 25:S1534-5807(24)00324-1. doi: 10.1016/j.devcel.2024.05.007.
Tingting Zhang 1,  Chenxi Zhao 1,  Yunxuan Li 1,  Jie Wu 1,  Feng Wang 1,  Jinmei Yu 2,  Zhenhe Wang 2,  Yang Gao 1,  Luyao Zhao 1,  Ying Liu 1,  Yechao Yan 1,  Xia Li 3,  Huan Gao 3,  Zhuowei Hu 2,  Bing Cui 4,  Ke Li 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences & Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 3 Marine College, Shandong University, Weihai 264200, China.
  • 4 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Chinese Academy of Medical Sciences & Peking Union Medical College, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: cuibing@imm.ac.cn.
  • 5 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: like1986@163.com.
PMID: 38821057 DOI: 10.1016/j.devcel.2024.05.007
Abstract

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-1α-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.

Keywords

CXCL14; FGD5; HIF-1α; Hedgehog; Rho guanine-nucleotide exchange factor; basal cell; endothelial cell; mammary gland; mammary microenvironment; reprogrammability.

Figures
Products