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

<jats:title>Abstract</jats:title><jats:p>The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals<jats:sup>1</jats:sup>. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,...

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Format: Article
Language:English
Published: Springer Science and Business Media LLC 2021
Online Access:https://hdl.handle.net/1721.1/138217
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collection MIT
description <jats:title>Abstract</jats:title><jats:p>The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals<jats:sup>1</jats:sup>. 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.</jats:p>
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spelling mit-1721.1/1382172021-11-24T03:18:17Z Comparative cellular analysis of motor cortex in human, marmoset and mouse <jats:title>Abstract</jats:title><jats:p>The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals<jats:sup>1</jats:sup>. 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.</jats:p> 2021-11-23T18:22:05Z 2021-11-23T18:22:05Z 2021-10-07 2021-11-23T18:03:54Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138217 2021. "Comparative cellular analysis of motor cortex in human, marmoset and mouse." Nature, 598 (7879). en 10.1038/s41586-021-03465-8 Nature Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Springer Science and Business Media LLC Nature
spellingShingle Comparative cellular analysis of motor cortex in human, marmoset and mouse
title Comparative cellular analysis of motor cortex in human, marmoset and mouse
title_full Comparative cellular analysis of motor cortex in human, marmoset and mouse
title_fullStr Comparative cellular analysis of motor cortex in human, marmoset and mouse
title_full_unstemmed Comparative cellular analysis of motor cortex in human, marmoset and mouse
title_short Comparative cellular analysis of motor cortex in human, marmoset and mouse
title_sort comparative cellular analysis of motor cortex in human marmoset and mouse
url https://hdl.handle.net/1721.1/138217