The role of Notch signaling in endometrial mesenchymal stromal/stem-like cells maintenance
Sisi Zhang, Rachel Chan, Ernest Hung Yu Ng, William S.B. Yeung
Abstract
Abstract Human endometrium undergoes cycles of regeneration in women of reproductive age. The endometrial mesenchymal stromal/stem cells (eMSC) contribute to this process. Notch signaling is essential for homeostasis of somatic stem cells. However, its role in eMSC remains unclear. We show with gain- and loss-of-function experiments that activation of Notch signaling promotes eMSC maintenance, while inhibition induces opposite effect. The activation of Notch signaling better maintains eMSC in a quiescent state. However, these quiescent eMSC can re-enter the cell cycle depending on the Notch and Wnt activities in the microenvironment, suggesting a crosstalk between the two signaling pathways. We further show that the Notch signaling is involved in endometrial remodeling event in a mouse menstrual-like model. Suppression of Notch signaling reduces the proliferation of Notch1 + label-retaining stromal cells and delays endometrial repair. Our data demonstrate the importance of Notch signaling in regulating the endometrial stem/progenitor cells in vitro and in vivo.