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Engineered Glycocalyx Regulates Stem Cell Proliferation in Murine Crypt Organoids
Sara H Rouhanifard1, Aime Lopez Aguilar2, Lu Meng3
1Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Cell Chemical Biology
|February 13, 2018
Summary
Paneth cells in the gut express N-acetyllactosamine (LacNAc) glycans. Blocking these LacNAc glycans on Paneth cells causes Lgr5+ stem cells to over-proliferate, revealing a role for glycans in stem cell regulation.
Area of Science:
- Gastroenterology
- Stem Cell Biology
- Glycobiology
Background:
- The intestinal crypt harbors Lgr5+ stem cells crucial for tissue regeneration.
- Paneth cells provide niche signals essential for Lgr5+ stem cell maintenance.
- Glycosylation patterns and their role in intestinal stem cell regulation are not well understood.
Purpose of the Study:
- To investigate the role of N-acetyllactosamine (LacNAc) glycans in the intestinal crypt niche.
- To determine the impact of LacNAc on Lgr5+ stem cell proliferation and differentiation.
Main Methods:
- Enzymatic glycan editing in cultured intestinal crypt organoids.
- Analysis of Paneth cell and Lgr5+ stem cell glycosylation patterns.
- Assessment of Lgr5+ stem cell proliferation and gene expression.
Main Results:
- Paneth cells, but not Lgr5+ stem cells, exhibit abundant terminal LacNAc.
- Blocking LacNAc on Paneth cells induces hyperproliferation of Lgr5+ stem cells.
- This hyperproliferation is associated with downregulation of proliferation inhibitors.
Conclusions:
- Terminal LacNAc on Paneth cells plays a critical role in regulating Lgr5+ stem cell proliferation.
- Glycan-mediated signaling from Paneth cells is essential for maintaining intestinal stem cell homeostasis.
