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Publication : Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration.

First Author  Wang R Year  2021
Journal  Front Cell Dev Biol Volume  9
Pages  772669 PubMed ID  34805179
Mgi Jnum  J:366226 Mgi Id  MGI:6827875
Doi  10.3389/fcell.2021.772669 Citation  Wang R, et al. (2021) Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration. Front Cell Dev Biol 9:772669
abstractText  Programmed cell death ligand 1 (PD-L1) is widely expressed in a variety of human tumors, and inhibition of the PD-L1/PD-1 pathway represents one of the most promising therapy for many types of cancer. However, the physiological function of PD-L1 in tissue development is still unclear, although PD-L1 mRNA is abundant in many tissues. To address this puzzle, we investigated the function of PD-L1 in mammary gland development. Interestingly, we found that PD-L1 is enriched in protein C receptor (Procr)-expressing mammary stem cells (MaSCs), and PD-L1-expressing mammary basal cells (PD-L1(+) basal cells) exhibit robust mammary regeneration capacity in transplantation assay. The lineage tracing experiment showed that PD-L1(+) cells can differentiate into all lineages of mammary epithelium cells, suggesting that PD-L1(+) basal cells have the activities of MaSCs. Furthermore, PD-L1 deficiency significantly impairs mammary development and reduces mammary regeneration capacity of mammary basal cells, suggesting that PD-L1 is not only enriched in MaSCs but also improves activities of MaSCs. In summary, these results demonstrated that PD-L1 is enriched in MaSCs and promotes mammary gland development and regeneration. Mechanistically, our data indicated that PD-L1 expression is induced by continuous activation of Wnt/ss-catenin signaling. In conclusion, these results demonstrated that PD-L1 is a marker of MaSCs, and PD-L1 is essential for mammary development. Our study provides novel insight into the physiological functions of PD-L1 in tissue development.
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