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

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.

authors

Zhang ZN,Freitas BC,Qian H,Lux J,Acab A,Trujillo CA,Herai RH,Nguyen Huu VA,Wen JH,Joshi-Barr S,Karpiak JV,Engler AJ,Fu XD,Muotri AR,Almutairi A

doi

10.1073/pnas.1521255113

subject

Has Abstract

pub_date

2016-03-22 00:00:00

pages

3185-90

issue

12

eissn

0027-8424

issn

1091-6490

pii

1521255113

journal_volume

113

pub_type

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