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.
journal_name
Proc Natl Acad Sci U S Aauthors
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 Adoi
10.1073/pnas.1521255113subject
Has Abstractpub_date
2016-03-22 00:00:00pages
3185-90issue
12eissn
0027-8424issn
1091-6490pii
1521255113journal_volume
113pub_type
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