title: Drosophila perlecan regulates intestinal stem cell activity via cell-matrix attachment.
abstract: Stem cells require specialized local microenvironments, termed niches, for normal retention, proliferation, and multipotency. Niches are composed of cells together with their associated extracellular matrix (ECM). Currently, the roles of ECM in regulating niche functions are poorly understood. Here, we demonstrate that Perlecan (Pcan), a highly conserved ECM component, controls intestinal stem cell (ISC) activities and ISC-ECM attachment in Drosophila adult posterior midgut. Loss of Pcan from ISCs, but not other surrounding cells, causes ISCs to detach from underlying ECM, lose their identity, and fail to proliferate. These defects are not a result of a loss of epidermal growth factor receptor (EGFR) or Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling activity but partially depend on integrin signaling activity. We propose that Pcan secreted by ISCs confers niche properties to the adjacent ECM that is required for ISC maintenance of stem cell identity, activity, and anchorage to the niche.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA ; The Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: You
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Key Laboratory for Medical Genetics, School of Life Sciences, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Zhefeng
authors.initials: Z
authors.lastname: Lou
authors.affiliation: Zhejiang Provincial Key Laboratory for Medical Genetics, School of Life Sciences, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Longjin
authors.initials: L
authors.lastname: Jin
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA ; The Graduate Program in Molecular and Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA ; State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Science, Beijing 100101, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Lin
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D066246:ErbB Receptors