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Nature Papers Describe Method to Measure Proteins, RNA in Single Nuclei; Present Mammalian Motor Cortex Atlas

A new method for the joint measurement of quantitative protein and RNA levels in thousands of individual nuclei is presented in Nature Methods this week. The technique — called intranuclear cellular indexing of transcriptomes and epitopes or inCITE-seq — was developed by Broad Institute researchers and enables multiplexed and quantitative intranuclear protein measurements using DNA-conjugated antibodies coupled with RNA-seq on a droplet-based profiling platform. In the report, the scientists use inCITE-seq to profile the response to environmental stimuli in cells and tissues, first in a HeLa cell line responding to cytokine stimulation and then in the mouse brain after pharmacological treatment. The method, they write, "can illuminate how combinations of nuclear proteins shape gene expression in native tissue contexts, with direct applications to solid or frozen tissues and clinical specimens."

The first resource to be developed by the National Institutes of Health's BRAIN Initiative Cell Census Network (BICCN), a multimodal cell census and atlas of the mammalian primary motor cortex, is published in Nature this week. The atlas provides new insights into brain organization and was created through the coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. In a series of companion papers, BICCN members report a transcriptomic atlas of the mouse cerebellar cortex; an analysis revealing cell-type-specific chromatin accessibility patterns in the developing human brain; an atlas of cortical arealization in the human brain; the identification of extensive isoform diversity and cell-type specificity in the mouse primary motor cortex; a genetic dissection of the glutamatergic neuron system in mouse cerebral cortex; the creation and application of a pipeline to label, image, reconstruct and classify single neurons in mice; a study of epigenomic diversity of cortical projection neurons in the mouse brain; the mapping of the mouse cortico-basal ganglia-thalamic network; and a comprehensive cell type-based anatomical description of the mouse primary motor cortex, upper limb area. Also published are a spatially resolved cell atlas of the mouse primary motor cortex; an atlas of gene regulatory elements in the adult mouse cerebrum; a DNA methylation atlas of the mouse brain at single-cell resolution; a study identifying glutamatergic neuron diversification in human neocortical expansion; a comparative cellular analysis of the human, marmoset, and mouse motor cortex; and a transcriptomic and epigenomic cell atlas of the mouse primary motor cortex.