Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells
The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood–brain barrier and carry a cell...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/7/3575 |
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| author | Gabriela Xavier Alexander Navarrete Santos Carla Hartmann Marcos L. Santoro Nicole Flegel Jessica Reinsch Annika Majer Toni Ehrhardt Jenny Pfeifer Andreas Simm Thomas Hollemann Sintia I. Belangero Dan Rujescu Matthias Jung |
| author_facet | Gabriela Xavier Alexander Navarrete Santos Carla Hartmann Marcos L. Santoro Nicole Flegel Jessica Reinsch Annika Majer Toni Ehrhardt Jenny Pfeifer Andreas Simm Thomas Hollemann Sintia I. Belangero Dan Rujescu Matthias Jung |
| author_sort | Gabriela Xavier |
| collection | DOAJ |
| description | The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood–brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells. Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). To identify molecular fingerprints associated with disease, circulating exosomes derived from healthy control (HC) individuals were compared against schizophrenia (SCZ) patients and late-onset Alzheimer’s disease (LOAD) patients. A significant epitope pattern was identified for LOAD (CD1c and CD2) but not for SCZ compared to HC. Thus, analysis of cell type- and disease-specific exosome signatures of iPSC-derived cell cultures may provide a valuable model system to explore proteomic biomarkers for the identification of novel disease profiles. |
| first_indexed | 2024-04-24T10:44:53Z |
| format | Article |
| id | doaj.art-c36f6bf669684962a19fe94934e282f0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-04-24T10:44:53Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c36f6bf669684962a19fe94934e282f02024-04-12T13:19:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-03-01257357510.3390/ijms25073575Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain CellsGabriela Xavier0Alexander Navarrete Santos1Carla Hartmann2Marcos L. Santoro3Nicole Flegel4Jessica Reinsch5Annika Majer6Toni Ehrhardt7Jenny Pfeifer8Andreas Simm9Thomas Hollemann10Sintia I. Belangero11Dan Rujescu12Matthias Jung13LiNC—Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo CEP 05039-032, BrazilCentre for Medical Basic Research, Medical Faculty, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyLiNC—Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo CEP 05039-032, BrazilInstitute for Biochemistry, Friedrich Alexander University Erlangen-Nürnberg, 91054 Erlangen, GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyClinic for Cardiac and Thoracic Surgery, Martin Luther University Halle-Wittenberg, 06120 Halle (Saale), GermanyInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyLiNC—Laboratory of Integrative Neuroscience, Universidade Federal de São Paulo (UNIFESP), São Paulo CEP 05039-032, BrazilDepartment of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, AustriaInstitute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, 06114 Halle (Saale), GermanyThe pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood–brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells. Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). To identify molecular fingerprints associated with disease, circulating exosomes derived from healthy control (HC) individuals were compared against schizophrenia (SCZ) patients and late-onset Alzheimer’s disease (LOAD) patients. A significant epitope pattern was identified for LOAD (CD1c and CD2) but not for SCZ compared to HC. Thus, analysis of cell type- and disease-specific exosome signatures of iPSC-derived cell cultures may provide a valuable model system to explore proteomic biomarkers for the identification of novel disease profiles.https://www.mdpi.com/1422-0067/25/7/3575extracellular vesicles (EVs)induced pluripotent stem cells (iPSCs)neural differentiationastrocytesbrain capillary endothelial cells (BCECs)schizophrenia |
| spellingShingle | Gabriela Xavier Alexander Navarrete Santos Carla Hartmann Marcos L. Santoro Nicole Flegel Jessica Reinsch Annika Majer Toni Ehrhardt Jenny Pfeifer Andreas Simm Thomas Hollemann Sintia I. Belangero Dan Rujescu Matthias Jung Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells International Journal of Molecular Sciences extracellular vesicles (EVs) induced pluripotent stem cells (iPSCs) neural differentiation astrocytes brain capillary endothelial cells (BCECs) schizophrenia |
| title | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells |
| title_full | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells |
| title_fullStr | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells |
| title_full_unstemmed | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells |
| title_short | Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells |
| title_sort | comparison of extracellular vesicles from induced pluripotent stem cell derived brain cells |
| topic | extracellular vesicles (EVs) induced pluripotent stem cells (iPSCs) neural differentiation astrocytes brain capillary endothelial cells (BCECs) schizophrenia |
| url | https://www.mdpi.com/1422-0067/25/7/3575 |
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