Microvesicle-mediated Wnt/β-Catenin Signaling Promotes Interspecies Mammary Stem/Progenitor Cell Growth

Area of Science:

• Cell Biology
• Stem Cell Biology
• Developmental Biology

Background:

• Mammary stem/progenitor cell (MaSC) self-renewal is crucial for mammary gland development and function.
• Equine MaSCs (eMaSCs) exhibit indefinite self-renewal potential in vitro, unlike canine MaSCs (cMaSCs).

Purpose of the Study:

• To investigate the role of microvesicles (MVs) in regulating MaSC self-renewal.
• To explore the mechanism by which eMaSCs promote self-renewal in cMaSCs.

Main Methods:

• Isolation and characterization of MVs from eMaSCs and cMaSCs.
• Analysis of Wnt protein expression in MVs.
• Assessment of Wnt/β-catenin signaling activation in target cells.
• Evaluation of mammosphere formation in cMaSCs treated with eMaSC-MVs.

Main Results:

• eMaSC-derived MVs contain higher levels of Wnt3a and Wnt1 compared to cMaSC-MVs.
• eMaSC-MVs induce prolonged Wnt/β-catenin signaling in cMaSCs, exceeding the effect of recombinant Wnt proteins.
• eMaSC-MVs significantly enhance cMaSC mammosphere formation, an effect blocked by Wnt inhibitors.

Conclusions:

• Microvesicles mediate intercellular communication crucial for MaSC self-renewal.
• eMaSC-MVs promote cMaSC self-renewal through sustained Wnt/β-catenin pathway activation.
• This study reveals a novel mechanism of stem cell regulation involving MV-mediated Wnt signaling.