We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Hypoxia Regulates the Self-Renewal of Endometrial Mesenchymal Stromal/Stem-like Cells via Notch Signaling.
- Authors
Zhang, Sisi; Chan, Rachel W.S.; Ng, Ernest H.Y.; Yeung, William S.B.
- Abstract
Human endometrium is an incredibly dynamic tissue undergoing cyclic regeneration and shedding during a woman's reproductive life. Endometrial mesenchymal stromal/stem-like cells (eMSC) contribute to this process. A hypoxic niche with low oxygen levels has been reported in multiple somatic stem cell types. However, the knowledge of hypoxia on eMSC remains limited. In mice, stromal stem/progenitor cells can be identified by the label-retaining technique. We examined the relationship between the label-retaining stromal cells (LRSC) and hypoxia during tissue breakdown in a mouse model of simulated menses. Our results demonstrated that LRSC resided in a hypoxic microenvironment during endometrial breakdown and early repair. Immunofluorescence staining revealed that the hypoxic-located LRSC underwent proliferation and was highly colocalized with Notch1. In vitro studies illustrated that hypoxia activated Notch signaling in eMSC, leading to enhanced self-renewal, clonogenicity and proliferation of cells. More importantly, HIF-1α played an essential role in the hypoxia-mediated maintenance of eMSC through the activation of Notch signaling. In conclusion, our findings show that some endometrial stem/progenitor cells reside in a hypoxic niche during menstruation, and hypoxia can regulate the self-renewal activity of eMSC via Notch signaling.
- Subjects
ENDOMETRIUM; HYPOXEMIA; PROGENITOR cells; NOTCH genes; SOMATIC cells; STROMAL cells; STEM cells
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 9, p4613
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23094613