A developmental atlas of the mouse brain by single-cell mass cytometry

Abstract

Development of the mammalian brain requires precisely controlled differentiation of neurons, glia, and nonneural cells. To investigate protein-level changes in these diverse cell types and their progenitors, we performed single-cell mass cytometry on whole brain (E11.5/E12.5) and microdissected telencephalon, diencephalon, mesencephalon, and rhombencephalon (E13.5-P4) collected at daily timepoints from C57/BL6 mice. Measuring 24,290,787 cells from 112 sample replicates with a 40-antibody panel, we quantified 85 molecularly distinct cell populations across embryonic and postnatal development, including microglia putatively phagocytosing neurites, neural cells, and myelin. Differentiation trajectory analysis also identified two separate pathways for producing oligodendrocyte precursor cells. Comparison with previous studies revealed considerable discrepancies between protein and mRNA abundances in the developing brain, demonstrating the value of protein-level measurements for identifying functional cell states. Overall, our findings demonstrate the utility of mass cytometry as a high-throughput, scalable platform for single-cell profiling of brain tissue.

GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data

“…The four GBM cell types described by Neftel et al are delineated by gene expression [19]. Recent studies have shown that such transcriptional cell-type markers often do not translate to protein level markers for use in approaches such as IMC[13, 32]. We set out to test this for the GBM neoplastic cell types, specifically.…”

Cell-Type-Specific Neuroproteomics of Synapses

“…Imaging mass cytometry (IMC) with IMS is another approach that can be used to study cell types, subcellular compartments, and cell-type-specific synapses [2]. IMC uses antibodies coupled to heavy metal species to label proteins, allowing the simultaneous imaging of up to 40 different proteins, with labeled proteins identified by IMS [135,136]. In Van Deusen et al, protein-based cell atlases of the developing mouse telencephalon, diencephalon, mesencephalon, and rhombencephalon were mapped using this approach.…”

“…In Van Deusen et al, protein-based cell atlases of the developing mouse telencephalon, diencephalon, mesencephalon, and rhombencephalon were mapped using this approach. They quantified 85 molecularly distinct cell populations, including neurons and myelin [136].…”