Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons

Human induced pluripotent stem cells (hiPSCs) are a suitable tool to study basic molecular and cellular mechanisms of neurodevelopment. The directed differentiation of hiPSCs via the generation of a self-renewable neuronal precursor cell line allows the standardization of defined differentiation pro...

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Main Authors: Sandra Horschitz, Friederike Matthäus, Anja Groß, Jan Rosner, Marta Galach, Wolfgang Greffrath, Rolf-Detlef Treede, Jochen Utikal, Patrick Schloss, Andreas Meyer-Lindenberg
Format: Article
Language:English
Published: Elsevier 2015-07-01
Series:Stem Cell Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1873506115000495
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author Sandra Horschitz
Friederike Matthäus
Anja Groß
Jan Rosner
Marta Galach
Wolfgang Greffrath
Rolf-Detlef Treede
Jochen Utikal
Patrick Schloss
Andreas Meyer-Lindenberg
author_facet Sandra Horschitz
Friederike Matthäus
Anja Groß
Jan Rosner
Marta Galach
Wolfgang Greffrath
Rolf-Detlef Treede
Jochen Utikal
Patrick Schloss
Andreas Meyer-Lindenberg
author_sort Sandra Horschitz
collection DOAJ
description Human induced pluripotent stem cells (hiPSCs) are a suitable tool to study basic molecular and cellular mechanisms of neurodevelopment. The directed differentiation of hiPSCs via the generation of a self-renewable neuronal precursor cell line allows the standardization of defined differentiation protocols. Here, we have investigated whether preconditioning with retinoic acid during early neural induction impacts on morphological and functional characteristics of the neuronal culture after terminal differentiation. For this purpose we have analyzed neuronal and glial cell markers, neuronal outgrowth, soma size, depolarization-induced distal shifts of the axon initial segment as well as glutamate-evoked calcium influx. Retinoic acid preconditioning led to a higher yield of neurons vs. glia cells and longer axons than unconditioned controls. In contrast, glutamatergic activation and depolarization induced structural plasticity were unchanged. Our results show that the treatment of neuroectodermal cells with retinoic acid during early development, i.e. during the neurulation phase, increases the yield of neuronal phenotypes, but does not impact on the functionality of terminally differentiated neuronal cells.
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spelling doaj.art-6b221c77d87540ab88404c9d6e1133c82022-12-22T02:34:10ZengElsevierStem Cell Research1873-50611876-77532015-07-01151304110.1016/j.scr.2015.04.007Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neuronsSandra Horschitz0Friederike Matthäus1Anja Groß2Jan Rosner3Marta Galach4Wolfgang Greffrath5Rolf-Detlef Treede6Jochen Utikal7Patrick Schloss8Andreas Meyer-Lindenberg9Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanySkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, University of Heidelberg/Medical Faculty Mannheim, Mannheim, GermanyDepartment of Neurophysiology, Center for Biomedicine and Medical Technology Mannheim, University of Heidelberg/Medical Faculty Mannheim, Mannheim, GermanySkin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg/Medical Faculty Mannheim, GermanyHuman induced pluripotent stem cells (hiPSCs) are a suitable tool to study basic molecular and cellular mechanisms of neurodevelopment. The directed differentiation of hiPSCs via the generation of a self-renewable neuronal precursor cell line allows the standardization of defined differentiation protocols. Here, we have investigated whether preconditioning with retinoic acid during early neural induction impacts on morphological and functional characteristics of the neuronal culture after terminal differentiation. For this purpose we have analyzed neuronal and glial cell markers, neuronal outgrowth, soma size, depolarization-induced distal shifts of the axon initial segment as well as glutamate-evoked calcium influx. Retinoic acid preconditioning led to a higher yield of neurons vs. glia cells and longer axons than unconditioned controls. In contrast, glutamatergic activation and depolarization induced structural plasticity were unchanged. Our results show that the treatment of neuroectodermal cells with retinoic acid during early development, i.e. during the neurulation phase, increases the yield of neuronal phenotypes, but does not impact on the functionality of terminally differentiated neuronal cells.http://www.sciencedirect.com/science/article/pii/S1873506115000495
spellingShingle Sandra Horschitz
Friederike Matthäus
Anja Groß
Jan Rosner
Marta Galach
Wolfgang Greffrath
Rolf-Detlef Treede
Jochen Utikal
Patrick Schloss
Andreas Meyer-Lindenberg
Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
Stem Cell Research
title Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
title_full Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
title_fullStr Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
title_full_unstemmed Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
title_short Impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell-derived neurons
title_sort impact of preconditioning with retinoic acid during early development on morphological and functional characteristics of human induced pluripotent stem cell derived neurons
url http://www.sciencedirect.com/science/article/pii/S1873506115000495
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