Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells

Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on p...

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Main Authors: Jing Yang Tee, Alan Mackay-Sim
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/17/9177
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author Jing Yang Tee
Alan Mackay-Sim
author_facet Jing Yang Tee
Alan Mackay-Sim
author_sort Jing Yang Tee
collection DOAJ
description Cell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.
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spelling doaj.art-04457487aa574561aff0ad040cf8b4162023-11-22T10:39:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217917710.3390/ijms22179177Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory CellsJing Yang Tee0Alan Mackay-Sim1Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, AustraliaGriffith Institute for Drug Discovery, Griffith University, Nathan, QLD 4111, AustraliaCell migration is critical for brain development and linked to several neurodevelopmental disorders, including schizophrenia. We have shown previously that cell migration is dysregulated in olfactory neural stem cells from people with schizophrenia. Although they moved faster than control cells on plastic substrates, patient cells were insensitive to regulation by extracellular matrix proteins, which increase the speeds of control cells. As well as speed, cell migration is also described by directional persistence, the straightness of movement. The aim of this study was to determine whether directional persistence is dysregulated in schizophrenia patient cells and whether it is modified on extracellular matrix proteins. Directional persistence in patient-derived and control-derived olfactory cells was quantified from automated live-cell imaging of migrating cells. On plastic substrates, patient cells were more persistent than control cells, with straighter trajectories and smaller turn angles. On most extracellular matrix proteins, persistence increased in patient and control cells in a concentration-dependent manner, but patient cells remained more persistent. Patient cells therefore have a subtle but complex phenotype in migration speed and persistence on most extracellular matrix protein substrates compared to control cells. If present in the developing brain, this could lead to altered brain development in schizophrenia.https://www.mdpi.com/1422-0067/22/17/9177schizophreniadisease modelingpatient-derived cell modelcell migrationlive cell imagingextracellular matrix
spellingShingle Jing Yang Tee
Alan Mackay-Sim
Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
International Journal of Molecular Sciences
schizophrenia
disease modeling
patient-derived cell model
cell migration
live cell imaging
extracellular matrix
title Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
title_full Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
title_fullStr Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
title_full_unstemmed Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
title_short Directional Persistence of Cell Migration in Schizophrenia Patient-Derived Olfactory Cells
title_sort directional persistence of cell migration in schizophrenia patient derived olfactory cells
topic schizophrenia
disease modeling
patient-derived cell model
cell migration
live cell imaging
extracellular matrix
url https://www.mdpi.com/1422-0067/22/17/9177
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AT alanmackaysim directionalpersistenceofcellmigrationinschizophreniapatientderivedolfactorycells