The Role of Notch Signaling in Endometrial Mesenchymal Stromal/Stem-like Cells Maintenance

Abstract

Human endometrium undergoes cycles of regeneration in reproductive women. The endometrial mesenchymal stromal/stem cells (eMSC) contribute to this process. Notch signaling is essential for the homeostasis of somatic stem cells. However, its role in eMSC remains unclear. The gain and loss function shows that activation of Notch signaling promotes eMSC maintenance, while inhibition displays opposite effect. Activation of Notch pathway better maintains eMSC in a quiescent state. However, these quiescent eMSC can re-enter into the cell cycle depending on Notch and Wnt activity in the microenvironment, suggesting a crosstalk between two signaling pathways. In a mouse menstrual-like model, we observe that Notch signaling is highly involved in the dynamic endometrial remodeling event. Suppression of Notch signaling significantly reduces the proliferation of Notch1+ label-retaining stromal cells and consequently delays the endometrial repair. Our data demonstrate the importance of Notch signaling in regulating the endometrial stem/progenitor cells in vitro and in vivo.