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• W2153453036 abstract "The exquisite control of growth factor function by heparan sulfate (HS) is dictated by tremendous structural heterogeneity of sulfated modifications. How specific HS structures control growth factor-dependent progenitor expansion during organogenesis is unknown. We isolated KIT+ progenitors from fetal salivary glands during a stage of rapid progenitor expansion and profiled HS biosynthetic enzyme expression. Enzymes generating a specific type of 3-O-sulfated-HS (3-O-HS) are enriched, and fibroblast growth factor 10 (FGF10)/FGF receptor 2b (FGFR2b) signaling directly regulates their expression. Bioengineered 3-O-HS binds FGFR2b and stabilizes FGF10/FGFR2b complexes in a receptor- and growth factor-specific manner. Rapid autocrine feedback increases 3-O-HS, KIT, and progenitor expansion. Knockdown of multiple Hs3st isoforms limits fetal progenitor expansion but is rescued with bioengineered 3-O-HS, which also increases adult progenitor expansion. Altering specific 3-O-sulfated epitopes provides a mechanism to rapidly respond to FGFR2b signaling and control progenitor expansion. 3-O-HS may expand KIT+ progenitors in vitro for regenerative therapy." @default.
• W2153453036 created "2016-06-24" @default.
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• W2153453036 date "2014-06-01" @default.
• W2153453036 modified "2023-10-15" @default.
• W2153453036 title "Hs3st3-Modified Heparan Sulfate Controls KIT+ Progenitor Expansion by Regulating 3-O-Sulfotransferases" @default.
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• W2153453036 doi "https://doi.org/10.1016/j.devcel.2014.04.024" @default.
• W2153453036 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4105206" @default.
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• W2153453036 hasPublicationYear "2014" @default.
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