Abstract Background The BIN1 locus contains the second-most significant genetic risk factor for late-onset Alzheimer’s disease. BIN1 undergoes alternate splicing to generate tissue- and cell-type-specific BIN1 isoforms, which regulate membrane dynamics in a range of crucial cellular processes. Whilst the expression of BIN1 in the brain has been characterized in neurons and oligodendrocytes in detail, information regarding microglial BIN1 expression is mainly limited to large-scale transcriptomic and proteomic data. Notably, BIN1 protein expression and its functional roles in microglia, a cell type most relevant to Alzheimer’s disease, have not been examined in depth. Methods Microglial BIN1 expression was analyzed bymore »
This content will become publicly available on December 1, 2022
Resolving cell state in iPSC-derived human neural samples with multiplexed fluorescence imaging
Abstract Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization of the spatial-temporal evolution of cell state in 3D culture and subsequent 2D dissociated culture models based on protein expression levels and localizations is essential to understanding neural cell differentiation, disease state phenotypes, and sample-to-sample variability. Here, we apply PR obe-based I maging for S equential M ultiplexing (PRISM) to facilitate multiplexed imaging with facile, rapid exchange of imaging probes to analyze iPSC-derived cortical and motor neuron cultures that are relevant to psychiatric and neurodegenerative disease models, using over ten protein targets. Our approach permits analysis of cell differentiation, cell composition, and functional marker expression in complex stem-cell derived neural cultures. Furthermore, our approach is amenable to automation, offering in principle the ability to scale-up to dozens of protein targets and samples.
- Award ID(s):
- 1707999
- Publication Date:
- NSF-PAR ID:
- 10283619
- Journal Name:
- Communications Biology
- Volume:
- 4
- Issue:
- 1
- ISSN:
- 2399-3642
- Sponsoring Org:
- National Science Foundation
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