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dc.rights.licenseCC BY — Creative Commons Attribution
dc.contributor.authorPatel, Vaishali N.
dc.contributor.authorPineda, Dallas L.
dc.contributor.authorBerenstein, Elsa
dc.contributor.authorHauser, Belinda R.
dc.contributor.authorChoi, Sophie
dc.contributor.authorProchazkova, Michaela
dc.contributor.authorZheng, Changyu
dc.contributor.authorGoldsmith, Corinne M.
dc.contributor.authorvan Kuppevelt, Toin H.
dc.contributor.authorKulkarni, Ashok
dc.contributor.authorSong, Yuefan
dc.contributor.authorLinhardt, Robert J.
dc.contributor.authorChibly, Alejandro M.
dc.contributor.authorHoffman, Matthew P.
dc.identifier.citationLoss of Hs3st3a1 or Hs3st3b1 enzymes alters heparan sulfate to reduce epithelial morphogenesis and adult salivary gland function, V. N. Patel, D. L. Pineda, E. Berenstein, B. R. Hauser, S. Choi, M. Prochazkova, C. Zheng, C. M. Goldsmith, T. van Kuppevelt, A. Kulkarni, Y. Song, R. J. Linhardt, A. M. Chibly, M. P. Hoffman, Matrix Biology, 103-104, 37-57, 2021.
dc.descriptionMatrix Biology, 103-104, 37-57
dc.descriptionNote : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
dc.description.abstractHeparan sulfate 3-O-sulfotransferases generate highly sulfated but rare 3-O-sulfated heparan sulfate (HS) epitopes on cell surfaces and in the extracellular matrix. Previous ex vivo experiments suggested functional redundancy exists among the family of seven enzymes but that Hs3st3a1 and Hs3st3b1 sulfated HS increases epithelial FGFR signaling and morphogenesis. Single-cell RNAseq analysis of control SMGs identifies increased expression of Hs3st3a1 and Hs3st3b1 in endbud and myoepithelial cells, both of which are progenitor cells during development and regeneration. To analyze their in vivo functions, we generated both Hs3st3a1−/- and Hs3st3b1−/- single knockout mice, which are viable and fertile. Salivary glands from both mice have impaired fetal epithelial morphogenesis when cultured with FGF10. Hs3st3b1−/- mice have reduced intact SMG branching morphogenesis and reduced 3-O-sulfated HS in the basement membrane. Analysis of HS biosynthetic enzyme transcription highlighted some compensatory changes in sulfotransferases expression early in development. The overall glycosaminoglycan composition of adult control and KO mice were similar, although HS disaccharide analysis showed increased N- and non-sulfated disaccharides in Hs3st3a1−/− HS. Analysis of adult KO gland function revealed normal secretory innervation, but without stimulation there was an increase in frequency of drinking behavior in both KO mice, suggesting basal salivary hypofunction, possibly due to myoepithelial dysfunction. Understanding how 3-O-sulfation regulates myoepithelial progenitor function will be important to manipulate HS-binding growth factors to enhance tissue function and regeneration.
dc.description.sponsorshipNational Institutes of Health
dc.relation.ispartofThe Linhardt Research Labs Online Collection
dc.relation.ispartofRensselaer Polytechnic Institute, Troy, NY
dc.relation.ispartofMatrix Biology
dc.rightsAttribution 3.0 United States*
dc.subjectChemistry and chemical biology
dc.subjectChemical and biological engineering
dc.subjectBiomedical engineering
dc.titleLoss of Hs3st3a1 or Hs3st3b1 enzymes alters heparan sulfate to reduce epithelial morphogenesis and adult salivary gland functionen_US
dcterms.accessRightsOpen Access
dcterms.accessRightsA full text version is available in DSpace@RPI
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dc.relation.departmentThe Linhardt Research Labs.
dc.relation.departmentThe Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)

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CC BY — Creative Commons Attribution
Except where otherwise noted, this item's license is described as CC BY — Creative Commons Attribution