Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model

• DOI: 10.1038/s41467-022-34005-1
• Publication Date: 2022-10-21T14:08:47Z
• Authors: Hannah Drew Rickner; Lulu Jiang; Rui Hong; Nicholas K. O’Neill; Chromewell A. Mojica; Benjamin J. Snyder; Lushuang Zhang; Dipan Shaw; Maria Medalla; Benjamin Wolozin; Christine S. Cheng
• Keywords: Astrogliosis; Tauopathy

Abstract The use of iPSC derived brain organoid models to study neurodegenerative disease has been hampered by a lack systems that accurately and expeditiously recapitulate pathogenesis in the context neuron-glial interactions. Here we report development system, termed AstTau, which propagates toxic human tau oligomers neuron-astrocyte assembloids. AstTau system develops much neuronal astrocytic pathology observed tauopathies including misfolded, phosphorylated, oligomeric, fibrillar tau, strong neurodegeneration, reactive astrogliosis. Single cell transcriptomic profiling combined with immunochemistry characterizes model can more closely late-stage changes adult neurodegeneration. studies demonstrate striking neuroinflammatory heat shock protein (HSP) chaperone process. Treatment HSP90 inhibitor PU-H71 is used address putative dysfunctional HSP produces reduction highlighting potential as rapid reproducible tool for drug discovery.