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Proteomic alterations and novel markers of neurotoxic reactive astrocytes in human iPSC models

ABSTRACT: 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-1a, 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 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-positive cells in post-mortem samples from people with Alzheimers disease. Moreover, our whole cell 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.

INSTRUMENT(S): Offline basic pH RPLC with a XBridge C18 column

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Valentina Fossati

PROVIDER: MSV000088799 | MassIVE | Tue Feb 08 09:50:00 GMT 2022

REPOSITORIES: MassIVE

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