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Neural commitment of human pluripotent stem cells under defined conditions recapitulates neural development and generates patient‐specific neural cells
Author(s) -
Fernandes Tiago G.,
Duarte Sofia T.,
Ghazvini Mehrnaz,
Gaspar Cláudia,
Santos Diana C.,
Porteira Ana R.,
Rodrigues Gonçalo M. C.,
Haupt Simone,
Rombo Diogo M.,
Armstrong Judith,
Sebastião Ana M.,
Gribnau Joost,
GarciaCazorla Àngels,
Brüstle Oliver,
Henrique Domingos,
Cabral Joaquim M. S.,
Diogo Maria Margarida
Publication year - 2015
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.201400751
Subject(s) - induced pluripotent stem cell , neural stem cell , neurosphere , neural development , neural cell , neuroscience , biology , embryonic stem cell , microbiology and biotechnology , stem cell , cell , adult stem cell , genetics , gene
Standardization of culture methods for human pluripotent stem cell (PSC) neural differentiation can greatly contribute to the development of novel clinical advancements through the comprehension of neurodevelopmental diseases. Here, we report an approach that reproduces neural commitment from human induced pluripotent stem cells using dual‐SMAD inhibition under defined conditions in a vitronectin‐based monolayer system. By employing this method it was possible to obtain neurons derived from both control and Rett syndrome patients' pluripotent cells. During differentiation mutated cells displayed alterations in the number of neuronal projections, and production of Tuj1 and MAP2‐positive neurons. Although investigation of a broader number of patients would be required, these observations are in accordance with previous studies showing impaired differentiation of these cells. Consequently, our experimental methodology was proved useful not only for the generation of neural cells, but also made possible to compare neural differentiation behavior of different cell lines under defined culture conditions. This study thus expects to contribute with an optimized approach to study the neural commitment of human PSCs, and to produce patient‐specific neural cells that can be used to gain a better understanding of disease mechanisms.