학술논문

Brain-wide correspondence of neuronal epigenomics and distant projections.
Document Type
article
Source
Nature. 624(7991)
Subject
Animals
Mice
Amygdala
Brain
Consensus Sequence
Datasets as Topic
Epigenomics
Gene Expression Profiling
Hypothalamus
Mesencephalon
Neural Pathways
Neurons
Neurotransmitter Agents
Regulatory Sequences
Nucleic Acid
Rhombencephalon
Single-Cell Analysis
Thalamus
Transcription Factors
Language
Abstract
Single-cell analyses parse the brains billions of neurons into thousands of cell-type clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. We provide an overall synthesis with 926 statistical comparisons of discriminability of neurons projecting to each target for every source. We integrate this dataset into the larger BRAIN Initiative Cell Census Network atlas, composed of millions of neurons, to link projection cell types to consensus clusters. Integration with spatial transcriptomics further assigns projection-enriched clusters to smaller source regions than the original dissections. We exemplify this by presenting in-depth analyses of projection neurons from the hypothalamus, thalamus, hindbrain, amygdala and midbrain to provide insights into properties of those cell types, including differentially expressed genes, their associated cis-regulatory elements and transcription-factor-binding motifs, and neurotransmitter use.