Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models
Astrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q (“TIC”) has been...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.870085/full |
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| author | David Labib Zhen Wang Zhen Wang Priya Prakash Matthew Zimmer Matthew D. Smith Paul W. Frazel Lilianne Barbar Maria L. Sapar Peter A. Calabresi Peter A. Calabresi Junmin Peng Junmin Peng Junmin Peng Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Valentina Fossati |
| author_facet | David Labib Zhen Wang Zhen Wang Priya Prakash Matthew Zimmer Matthew D. Smith Paul W. Frazel Lilianne Barbar Maria L. Sapar Peter A. Calabresi Peter A. Calabresi Junmin Peng Junmin Peng Junmin Peng Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Valentina Fossati |
| author_sort | David Labib |
| collection | DOAJ |
| description | Astrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q (“TIC”) has been implicated in many neurodegenerative diseases as a source of neurotoxicity. Here, we used an established human induced pluripotent stem cell (hiPSC) model to investigate the surface marker profile and proteome of TIC-induced reactive astrocytes. We propose VCAM1, BST2, ICOSL, HLA-E, PD-L1, and PDPN as putative, novel markers of this reactive sub-state. We found that several of these markers colocalize with GFAP+ cells in post-mortem samples from people with Alzheimer’s disease. Moreover, our whole-cells proteomic analysis of TIC-induced reactive astrocytes identified proteins and related pathways primarily linked to potential engagement with peripheral immune cells. Taken together, our findings will serve as new tools to purify reactive astrocyte subtypes and to further explore their involvement in immune responses associated with injury and disease. |
| first_indexed | 2024-04-13T04:17:16Z |
| format | Article |
| id | doaj.art-22800728085c4e75a1250bbb8404609c |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T04:17:16Z |
| publishDate | 2022-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-22800728085c4e75a1250bbb8404609c2022-12-22T03:02:56ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-05-011510.3389/fnmol.2022.870085870085Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell ModelsDavid Labib0Zhen Wang1Zhen Wang2Priya Prakash3Matthew Zimmer4Matthew D. Smith5Paul W. Frazel6Lilianne Barbar7Maria L. Sapar8Peter A. Calabresi9Peter A. Calabresi10Junmin Peng11Junmin Peng12Junmin Peng13Shane A. Liddelow14Shane A. Liddelow15Shane A. Liddelow16Shane A. Liddelow17Valentina Fossati18The New York Stem Cell Foundation Research Institute, New York, NY, United StatesDepartment of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesNeuroscience Institute, NYU Grossman School of Medicine, New York, NY, United StatesThe New York Stem Cell Foundation Research Institute, New York, NY, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesNeuroscience Institute, NYU Grossman School of Medicine, New York, NY, United StatesThe New York Stem Cell Foundation Research Institute, New York, NY, United StatesThe New York Stem Cell Foundation Research Institute, New York, NY, United StatesDepartment of Neurology, Johns Hopkins University, Baltimore, MD, United StatesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, MD, United StatesDepartment of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Developmental Neurobiology, St. Jude Children’s Research Hospital, Memphis, TN, United StatesCenter for Proteomics and Metabolomics, St. Jude Children’s Research Hospital, Memphis, TN, United StatesNeuroscience Institute, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Neuroscience and Physiology, NYU Grossman School of Medicine, New York, NY, United StatesDepartment of Ophthalmology, NYU Grossman School of Medicine, New York, NY, United States0Parekh Center for Interdisciplinary Neurology, NYU Grossman School of Medicine, New York, NY, United StatesThe New York Stem Cell Foundation Research Institute, New York, NY, United StatesAstrocytes respond to injury, infection, and inflammation in the central nervous system by acquiring reactive states in which they may become dysfunctional and contribute to disease pathology. A sub-state of reactive astrocytes induced by proinflammatory factors TNF, IL-1α, and C1q (“TIC”) has been implicated in many neurodegenerative diseases as a source of neurotoxicity. Here, we used an established human induced pluripotent stem cell (hiPSC) model to investigate the surface marker profile and proteome of TIC-induced reactive astrocytes. We propose VCAM1, BST2, ICOSL, HLA-E, PD-L1, and PDPN as putative, novel markers of this reactive sub-state. We found that several of these markers colocalize with GFAP+ cells in post-mortem samples from people with Alzheimer’s disease. Moreover, our whole-cells proteomic analysis of TIC-induced reactive astrocytes identified proteins and related pathways primarily linked to potential engagement with peripheral immune cells. Taken together, our findings will serve as new tools to purify reactive astrocyte subtypes and to further explore their involvement in immune responses associated with injury and disease.https://www.frontiersin.org/articles/10.3389/fnmol.2022.870085/fullreactive astrocytesinduced pluripotent stem cellsproteomicssurface markersinflammationneurodegenerative diseases |
| spellingShingle | David Labib Zhen Wang Zhen Wang Priya Prakash Matthew Zimmer Matthew D. Smith Paul W. Frazel Lilianne Barbar Maria L. Sapar Peter A. Calabresi Peter A. Calabresi Junmin Peng Junmin Peng Junmin Peng Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Shane A. Liddelow Valentina Fossati Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models Frontiers in Molecular Neuroscience reactive astrocytes induced pluripotent stem cells proteomics surface markers inflammation neurodegenerative diseases |
| title | Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models |
| title_full | Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models |
| title_fullStr | Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models |
| title_full_unstemmed | Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models |
| title_short | Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models |
| title_sort | proteomic alterations and novel markers of neurotoxic reactive astrocytes in human induced pluripotent stem cell models |
| topic | reactive astrocytes induced pluripotent stem cells proteomics surface markers inflammation neurodegenerative diseases |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.870085/full |
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