Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
| Autor: | Wei Wei, Ruirui Wang, Cheguo Cai, Fujing Huang, Yu Zhou, Liya Yu, Junyuan Hu, Zi Ye |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
PD-L1
Messenger RNA Endothelial protein C receptor mammary regeneration mammary development QH301-705.5 Regeneration (biology) Wnt signaling pathway Cell Biology Biology Cell biology Cell and Developmental Biology Basal (phylogenetics) niche Mammary Epithelium biology.protein cross-talk Stem cell Biology (General) mammary stem cell Original Research Developmental Biology |
| Zdroj: | Frontiers in Cell and Developmental Biology, Vol 9 (2021) Frontiers in Cell and Developmental Biology |
| ISSN: | 2296-634X |
| DOI: | 10.3389/fcell.2021.772669 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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