PT  - JOURNAL ARTICLE
AU  - Hu Zeng
AU  - Jiahao Huang
AU  - Haowen Zhou
AU  - William J. Meilandt
AU  - Borislav Dejanovic
AU  - Yiming Zhou
AU  - Christopher J. Bohlen
AU  - Seung-Hye Lee
AU  - Jingyi Ren
AU  - Albert Liu
AU  - Hao Sheng
AU  - Jia Liu
AU  - Morgan Sheng
AU  - Xiao Wang
TI  - Integrative <em>in situ</em> mapping of single-cell transcriptional states and tissue histopathology in an Alzheimer’s disease model
AID  - 10.1101/2022.01.14.476072
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.01.14.476072
4099  - http://biorxiv.org/content/early/2022/01/16/2022.01.14.476072.short
4100  - http://biorxiv.org/content/early/2022/01/16/2022.01.14.476072.full
AB  - Amyloid-β plaques and neurofibrillary tau tangles are the neuropathologic hallmarks of Alzheimer’s disease (AD), but the spatiotemporal cellular responses and molecular mechanisms underlying AD pathophysiology remain poorly understood. Here we introduce STARmap PLUS to simultaneously map single-cell transcriptional states and disease marker proteins in brain tissues of AD mouse models at subcellular resolution (200 nm). This high-resolution spatial transcriptomics map revealed a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocytes (DAA) and oligodendrocyte precursor cells (OPC) are enriched in the outer shells surrounding the plaque- DAM complex. Hyperphosphorylated tau emerged mainly in excitatory neurons in the CA1 region accompanied by the infiltration of oligodendrocyte subtypes into the axon bundles of hippocampal alveus. The integrative STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing an unprecedented roadmap to pinpoint the molecular and cellular mechanisms of AD pathology and neurodegeneration.Competing Interest StatementX.W., H.Z., and J.R. are inventors on pending patent applications related to STARmap PLUS. W.J.M., C. J. B., and S.-H.L. are present employees of Genentech.