Functional Comparison of Blood-Derived Human Neural Progenitor Cells
Induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) are promising tools to model complex neurological or psychiatric diseases, including schizophrenia. Multiple studies have compared patient-derived and healthy control NPCs derived from iPSCs in order to investigate cellular...
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9118 |
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| author | Eszter Szabó Flóra Juhász Edit Hathy Dóra Reé László Homolya Zsuzsa Erdei János M. Réthelyi Ágota Apáti |
| author_facet | Eszter Szabó Flóra Juhász Edit Hathy Dóra Reé László Homolya Zsuzsa Erdei János M. Réthelyi Ágota Apáti |
| author_sort | Eszter Szabó |
| collection | DOAJ |
| description | Induced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) are promising tools to model complex neurological or psychiatric diseases, including schizophrenia. Multiple studies have compared patient-derived and healthy control NPCs derived from iPSCs in order to investigate cellular phenotypes of this disease, although the establishment, stabilization, and directed differentiation of iPSC lines are rather expensive and time-demanding. However, interrupted reprogramming by omitting the stabilization of iPSCs may allow for the generation of a plastic stage of the cells and thus provide a shortcut to derive NPSCs directly from tissue samples. Here, we demonstrate a method to generate shortcut NPCs (sNPCs) from blood mononuclear cells and present a detailed comparison of these sNPCs with NPCs obtained from the same blood samples through stable iPSC clones and a subsequent neural differentiation (classical NPCs—cNPCs). Peripheral blood cells were obtained from a schizophrenia patient and his two healthy parents (a case–parent trio), while a further umbilical cord blood sample was obtained from the cord of a healthy new-born. The expression of stage-specific markers in sNPCs and cNPCs were compared both at the protein and RNA levels. We also performed functional tests to investigate Wnt and glutamate signaling and the oxidative stress, as these pathways have been suggested to play important roles in the pathophysiology of schizophrenia. We found similar responses in the two types of NPCs, suggesting that the shortcut procedure provides sNPCs, allowing an efficient screening of disease-related phenotypes. |
| first_indexed | 2024-03-10T14:26:15Z |
| format | Article |
| id | doaj.art-7426c396ce0a43c398f9b50a90bc0642 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:26:15Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7426c396ce0a43c398f9b50a90bc06422023-11-20T22:59:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123911810.3390/ijms21239118Functional Comparison of Blood-Derived Human Neural Progenitor CellsEszter Szabó0Flóra Juhász1Edit Hathy2Dóra Reé3László Homolya4Zsuzsa Erdei5János M. Réthelyi6Ágota Apáti7Institute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, 1083 Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryDepartment of Psychiatry and Psychotherapy, Faculty of Medicine, Semmelweis University, 1083 Budapest, HungaryInstitute of Enzymology, Research Centre for Natural Sciences, 1117 Budapest, HungaryInduced pluripotent stem cell (iPSC)-derived neural progenitor cells (NPCs) are promising tools to model complex neurological or psychiatric diseases, including schizophrenia. Multiple studies have compared patient-derived and healthy control NPCs derived from iPSCs in order to investigate cellular phenotypes of this disease, although the establishment, stabilization, and directed differentiation of iPSC lines are rather expensive and time-demanding. However, interrupted reprogramming by omitting the stabilization of iPSCs may allow for the generation of a plastic stage of the cells and thus provide a shortcut to derive NPSCs directly from tissue samples. Here, we demonstrate a method to generate shortcut NPCs (sNPCs) from blood mononuclear cells and present a detailed comparison of these sNPCs with NPCs obtained from the same blood samples through stable iPSC clones and a subsequent neural differentiation (classical NPCs—cNPCs). Peripheral blood cells were obtained from a schizophrenia patient and his two healthy parents (a case–parent trio), while a further umbilical cord blood sample was obtained from the cord of a healthy new-born. The expression of stage-specific markers in sNPCs and cNPCs were compared both at the protein and RNA levels. We also performed functional tests to investigate Wnt and glutamate signaling and the oxidative stress, as these pathways have been suggested to play important roles in the pathophysiology of schizophrenia. We found similar responses in the two types of NPCs, suggesting that the shortcut procedure provides sNPCs, allowing an efficient screening of disease-related phenotypes.https://www.mdpi.com/1422-0067/21/23/9118neural progenitorsinterrupted reprogrammingiPSCneural differentiationschizophrenia |
| spellingShingle | Eszter Szabó Flóra Juhász Edit Hathy Dóra Reé László Homolya Zsuzsa Erdei János M. Réthelyi Ágota Apáti Functional Comparison of Blood-Derived Human Neural Progenitor Cells International Journal of Molecular Sciences neural progenitors interrupted reprogramming iPSC neural differentiation schizophrenia |
| title | Functional Comparison of Blood-Derived Human Neural Progenitor Cells |
| title_full | Functional Comparison of Blood-Derived Human Neural Progenitor Cells |
| title_fullStr | Functional Comparison of Blood-Derived Human Neural Progenitor Cells |
| title_full_unstemmed | Functional Comparison of Blood-Derived Human Neural Progenitor Cells |
| title_short | Functional Comparison of Blood-Derived Human Neural Progenitor Cells |
| title_sort | functional comparison of blood derived human neural progenitor cells |
| topic | neural progenitors interrupted reprogramming iPSC neural differentiation schizophrenia |
| url | https://www.mdpi.com/1422-0067/21/23/9118 |
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