title: Hs3st-A and Hs3st-B regulate intestinal homeostasis in Drosophila adult midgut.
abstract: Intrinsic and extrinsic signals as well as the extracellular matrix (ECM) tightly regulate stem cells for tissue homeostasis and regenerative capacity. Little is known about the regulation of tissue homeostasis by the ECM. Heparan sulfate proteoglycans (HSPGs), important components of the ECM, are involved in a variety of biological events. Two heparin sulfate 3-O sulfotransferase (Hs3st) genes, Hs3st-A and Hs3st-B, encode the modification enzymes in heparan sulfate (HS) biosynthesis. Here we demonstrate that Hs3st-A and Hs3st-B are required for adult midgut homeostasis. Depletion of Hs3st-A in enterocytes (ECs) results in increased intestinal stem cell (ISC) proliferation and tissue homeostasis loss. Moreover, increased ISC proliferation is also observed in Hs3st-B null mutant alone, or in combination with Hs3st-A RNAi. Hs3st-A depletion-induced ISC proliferation is effectively suppressed by simultaneous inhibition of the EGFR signaling pathway, suggesting that tissue homeostasis loss in Hs3st-A-deficient intestines is due to increased EGFR signaling. Furthermore, we find that Hs3st-A-depleted ECs are unhealthy and prone to death, while ectopic expression of the antiapoptotic p35 is able to greatly suppress tissue homeostasis loss in these intestines. Together, our data suggest that Drosophila Hs3st-A and Hs3st-B are involved in the regulation of ISC proliferation and midgut homeostasis maintenance.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; School of Life Sciences, Capital Normal University, Beijing 100048, China. Electronic address: zhouhua@ioz.ac.cn.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: xinhua.lin@ioz.ac.cn.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D006497:Heparan Sulfate / Q000096:biosynthesis / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D066246:ErbB Receptors; D006497:Heparan Sulfate; D018010:Receptors, Invertebrate Peptide; D015238:Sulfotransferases; C066532:Egfr protein, Drosophila; C021350:heparitin sulfotransferase
keywords: Drosophila; Heparan sulfate proteoglycans; Hs3st-A; Hs3st-B; Intestinal stem cell; Tissue homeostasis