Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models

David Labib, Zhen Wang, Priya Prakash, Matthew Zimmer, Matthew D. Smith, Paul W. Frazel, Lilianne Barbar, Maria L. Sapar, Peter A. Calabresi, Junmin Peng, Shane A. Liddelow, Valentina Fossati

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number870085
JournalFrontiers in Molecular Neuroscience
StatePublished - May 3 2022


  • induced pluripotent stem cells
  • inflammation
  • neurodegenerative diseases
  • proteomics
  • reactive astrocytes
  • surface markers

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology


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