Isoform cell-type specificity in the mouse primary motor cortex

A. Sina Booeshaghi, Zizhen Yao, Cindy Velthoven, Kimberly Smith, Bosiljka Tasic, Hongkui Zeng and Lior Pachter ()
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A. Sina Booeshaghi: California Institute of Technology
Zizhen Yao: Allen Institute for Brain Science
Cindy Velthoven: Allen Institute for Brain Science
Kimberly Smith: Allen Institute for Brain Science
Bosiljka Tasic: Allen Institute for Brain Science
Hongkui Zeng: Allen Institute for Brain Science
Lior Pachter: California Institute of Technology

Nature, 2021, vol. 598, issue 7879, 195-199

Abstract: Abstract Full-length SMART-seq1 single-cell RNA sequencing can be used to measure gene expression at isoform resolution, making possible the identification of specific isoform markers for different cell types. Used in conjunction with spatial RNA capture and gene-tagging methods, this enables the inference of spatially resolved isoform expression for different cell types. Here, in a comprehensive analysis of 6,160 mouse primary motor cortex cells assayed with SMART-seq, 280,327 cells assayed with MERFISH2 and 94,162 cells assayed with 10x Genomics sequencing3, we find examples of isoform specificity in cell types—including isoform shifts between cell types that are masked in gene-level analysis—as well as examples of transcriptional regulation. Additionally, we show that isoform specificity helps to refine cell types, and that a multi-platform analysis of single-cell transcriptomic data leveraging multiple measurements provides a comprehensive atlas of transcription in the mouse primary motor cortex that improves on the possibilities offered by any single technology.

Date: 2021
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DOI: 10.1038/s41586-021-03969-3

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