Cargando…

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

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. Her...

Descripción completa

Detalles Bibliográficos
Autores principales: Hyvärinen, Tanja, Hyysalo, Anu, Kapucu, Fikret Emre, Aarnos, Laura, Vinogradov, Andrey, Eglen, Stephen J., Ylä-Outinen, Laura, Narkilahti, Susanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868015/
https://www.ncbi.nlm.nih.gov/pubmed/31748598
http://dx.doi.org/10.1038/s41598-019-53647-8
_version_ 1783472173979009024
author Hyvärinen, Tanja
Hyysalo, Anu
Kapucu, Fikret Emre
Aarnos, Laura
Vinogradov, Andrey
Eglen, Stephen J.
Ylä-Outinen, Laura
Narkilahti, Susanna
author_facet Hyvärinen, Tanja
Hyysalo, Anu
Kapucu, Fikret Emre
Aarnos, Laura
Vinogradov, Andrey
Eglen, Stephen J.
Ylä-Outinen, Laura
Narkilahti, Susanna
author_sort Hyvärinen, Tanja
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6868015
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-68680152019-12-03 Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures Hyvärinen, Tanja Hyysalo, Anu Kapucu, Fikret Emre Aarnos, Laura Vinogradov, Andrey Eglen, Stephen J. Ylä-Outinen, Laura Narkilahti, Susanna Sci Rep Article 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. Nature Publishing Group UK 2019-11-20 /pmc/articles/PMC6868015/ /pubmed/31748598 http://dx.doi.org/10.1038/s41598-019-53647-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hyvärinen, Tanja
Hyysalo, Anu
Kapucu, Fikret Emre
Aarnos, Laura
Vinogradov, Andrey
Eglen, Stephen J.
Ylä-Outinen, Laura
Narkilahti, Susanna
Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title_full Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title_fullStr Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title_full_unstemmed Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title_short Functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
title_sort functional characterization of human pluripotent stem cell-derived cortical networks differentiated on laminin-521 substrate: comparison to rat cortical cultures
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868015/
https://www.ncbi.nlm.nih.gov/pubmed/31748598
http://dx.doi.org/10.1038/s41598-019-53647-8
work_keys_str_mv AT hyvarinentanja functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT hyysaloanu functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT kapucufikretemre functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT aarnoslaura functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT vinogradovandrey functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT eglenstephenj functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT ylaoutinenlaura functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures
AT narkilahtisusanna functionalcharacterizationofhumanpluripotentstemcellderivedcorticalnetworksdifferentiatedonlaminin521substratecomparisontoratcorticalcultures