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Indirect Immunofluorescence on Frozen Sections of Mouse Mammary Gland
Published on: December 1, 2015
Programmed Cell Death Ligand 1 Is Enriched in Mammary Stem Cells and Promotes Mammary Development and Regeneration
Ruirui Wang1, Fujing Huang1, Wei Wei1
1Department of Orthopaedics, Zhongnan Hospital of Wuhan University, Frontier Science Center for Immunology and Metabolism, Medical Research Institute, Wuhan University, Wuhan, China.
Abstract:
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.
Insights
Programmed cell death ligand 1 (PD-L1) is enriched in mammary stem cells (MaSCs) and essential for mammary gland development and regeneration. PD-L1 deficiency impairs mammary development, highlighting its crucial role in tissue homeostasis.
Area of Science:
- Developmental Biology
- Immunology
- Cancer Biology
Background:
- Programmed cell death ligand 1 (PD-L1) is a key immune checkpoint target in cancer therapy.
- Its physiological role in normal tissue development remains largely unknown despite abundant mRNA expression.
- Mammary gland development offers a model to study PD-L1's function in tissue homeostasis.
Purpose of the Study:
- To investigate the function of PD-L1 in mammary gland development and regeneration.
- To identify the specific cell populations expressing PD-L1 within the mammary gland.
- To elucidate the molecular mechanisms regulating PD-L1 expression in this context.
Main Methods:
- Mammary gland transplantation assays to assess regenerative capacity.
- Lineage tracing experiments to track cell differentiation.
- Analysis of PD-L1 expression in mammary stem cells (MaSCs) and basal cells.
- Genetic manipulation (PD-L1 deficiency) to study its functional impact.
- Investigation of Wnt/ß-catenin signaling pathway activation.
Main Results:
- PD-L1 is enriched in protein C receptor (Procr)-expressing MaSCs.
- PD-L1-expressing basal cells exhibit robust mammary regeneration capacity and differentiate into all mammary epithelial lineages.
- PD-L1 deficiency significantly impairs mammary gland development and reduces regenerative potential.
- PD-L1 expression is induced by sustained Wnt/ß-catenin signaling activation.
Conclusions:
- PD-L1 serves as a marker for MaSCs.
- PD-L1 is essential for normal mammary gland development and regeneration.
- PD-L1 plays a critical physiological role in tissue development beyond its function in cancer immunity.
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