Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate : comparison to rat cortical cultures

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http://hdl.handle.net/10138/311924

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Hyvärinen , T , Hyysalo , A , Kapucu , F E , Aarnos , L , Vinogradov , A , Eglen , S J , Ylä-Outinen , L & Narkilahti , S 2019 , ' Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate : comparison to rat cortical cultures ' , Scientific Reports , vol. 9 , 17125 . https://doi.org/10.1038/s41598-019-53647-8

Title: Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate : comparison to rat cortical cultures
Author: Hyvärinen, Tanja; Hyysalo, Anu; Kapucu, Fikret Emre; Aarnos, Laura; Vinogradov, Andrey; Eglen, Stephen J.; Ylä-Outinen, Laura; Narkilahti, Susanna
Contributor: University of Helsinki, Institute of Biotechnology
Date: 2019-11-20
Language: eng
Number of pages: 15
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/311924
Abstract: Human pluripotent stem cell (hPSC)-derived neurons provide exciting opportunities for in vitro modeling of neurological diseases and for advancing drug development and neurotoxicological studies. However, generating electrophysiologically mature neuronal networks from hPSCs has been challenging. Here, we report the differentiation of functionally active hPSC-derived cortical networks on defined laminin-521 substrate. We apply microelectrode array (MEA) measurements to assess network events and compare the activity development of hPSC-derived networks to that of widely used rat embryonic cortical cultures. In both of these networks, activity developed through a similar sequence of stages and time frames; however, the hPSC-derived networks showed unique patterns of bursting activity. The hPSC-derived networks developed synchronous activity, which involved glutamatergic and GABAergic inputs, recapitulating the classical cortical activity also observed in rodent counterparts. Principal component analysis (PCA) based on spike rates, network synchronization and burst features revealed the segregation of hPSC-derived and rat network recordings into different clusters, reflecting the species-specific and maturation state differences between the two networks. Overall, hPSC-derived neural cultures produced with a defined protocol generate cortical type network activity, which validates their applicability as a human-specific model for pharmacological studies and modeling network dysfunctions.
Subject: LONG-TERM POTENTIATION
ELECTRICAL-ACTIVITY
XENO-FREE
ACTIVITY PATTERNS
CEREBRAL-CORTEX
SPIKE DETECTION
NEURONS
DERIVATION
INDUCTION
LINES
3112 Neurosciences
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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