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Author (up) Zhang, Z.-N.; Freitas, B.C.; Qian, H.; Lux, J.; Acab, A.; Trujillo, C.A.; Herai, R.H.; Nguyen Huu, V.A.; Wen, J.H.; Joshi-Barr, S.; Karpiak, J.V.; Engler, A.J.; Fu, X.-D.; Muotri, A.R.; Almutairi, A. url  doi
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  Title Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction Type Journal Article
  Year 2016 Publication Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A  
  Volume 113 Issue 12 Pages 3185-3190  
  Keywords *Cell Movement; Humans; *Hydrogels; Induced Pluripotent Stem Cells/*cytology; Methyl-CpG-Binding Protein 2/*physiology; Neurons/*metabolism; 3D RTT modeling; 3D hydrogels; neuronal migration and maturation  
  Abstract Probing a wide range of cellular phenotypes in neurodevelopmental disorders using patient-derived neural progenitor cells (NPCs) can be facilitated by 3D assays, as 2D systems cannot entirely recapitulate the arrangement of cells in the brain. Here, we developed a previously unidentified 3D migration and differentiation assay in layered hydrogels to examine how these processes are affected in neurodevelopmental disorders, such as Rett syndrome. Our soft 3D system mimics the brain environment and accelerates maturation of neurons from human induced pluripotent stem cell (iPSC)-derived NPCs, yielding electrophysiologically active neurons within just 3 wk. Using this platform, we revealed a genotype-specific effect of methyl-CpG-binding protein-2 (MeCP2) dysfunction on iPSC-derived neuronal migration and maturation (reduced neurite outgrowth and fewer synapses) in 3D layered hydrogels. Thus, this 3D system expands the range of neural phenotypes that can be studied in vitro to include those influenced by physical and mechanical stimuli or requiring specific arrangements of multiple cell types.  
  Address Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093; aalmutairi@ucsd.edu muotri@ucsd.edu  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0027-8424 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26944080 Approved no  
  Call Number ref @ user @ Serial 95971  
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