Comparative cellular analysis of motor cortex in human, marmoset and mouse

By Trygve E Bakken, Nikolas L. Jorstad, Qiwen Hu, B. Lake, W. Tian, B. Kalmbach, M. Crow, R. Hodge, Fenna M. Krienen, S. Sorensen and 96 more. Nature, 2021

639 citations recorded by the source corpus.

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations. An examination of motor cortex in humans, marmosets and mice reveals a generally conserved cellular makeup that is likely to extend to many mammalian species, but also differences in gene expression, DNA methylation and chromatin state that lead to species-dependent specializations.

Subfields: Developmental Neuroscience, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/a10fe47a5709685797dca50f0164d7c142558b8b

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Dictionary learning for integrative, multimodal, and massively scalable single-cell analysis (2022, positive): “As a reference, we used a dataset from the Allen Brain Atlas, which defines an expertly curated and multilevel cell ontology 52 in the human cortex.”