Layered hydrogels accelerate iPSC-derived neuronal maturation and reveal migration defects caused by MeCP2 dysfunction

Zhen Ning Zhang, Beatriz C. Freitas, Hao Qian, Jacques Lux, Allan Acab, Cleber A. Trujillo, Roberto H. Herai, Viet Anh Nguyen Huu, Jessica H. Wen, Shivanjali Joshi-Barr, Jerome V. Karpiak, Adam J. Engler, Xiang Dong Fu, Alysson R. Muotri, Adah Almutairi

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3185-3190
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number12
DOIs
StatePublished - Mar 22 2016

Keywords

  • 3D RTT modeling
  • 3D hydrogels
  • Neuronal migration and maturation

ASJC Scopus subject areas

  • General

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