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| Status |
Public on Dec 24, 2020 |
| Title |
Phenotypic variation within and across transcriptomic cell types in mouse motor cortex |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Cortical neurons exhibit astounding diversity in gene expression as well as in morphological and electrophysiological properties. Most existing neural taxonomies are based on either transcriptomic or morpho-electric criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells. Here we used Patch-seq to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of over 1300 neurons in adult mouse motor cortex, providing a comprehensive morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (Vip, Pvalb, Sst, etc.) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well-separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neural types in the neocortex do not always form discrete entities. Instead, neurons follow a hierarchy consisting of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
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| Overall design |
Neurons from all layers of primary mouse motor cortex were profiled transcriptomically, electrophysiologically and morphologically using Patch-seq, using various Cre-driver lines to ensure a diverse sampling of known cell types. Neurons in acute slices were patch-clamped and stimulated with brief current impulses to record their electrophysiological activity, filled with biocytin for subsequent morphological recovery and reconstruction, and their RNA was extracted and sequenced.
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| Contributor(s) |
Hartmanis L, Sandberg R |
| Citation(s) |
33184512 |
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| Submission date |
Dec 23, 2020 |
| Last update date |
Feb 18, 2021 |
| Contact name |
Leonard Hartmanis |
| E-mail(s) |
leonard.hartmanis@ki.se
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| Organization name |
Karolinska Institutet
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| Department |
Cell & Molecular Biology
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| Lab |
Sandberg Lab
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| Street address |
Solnavägen 9
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| City |
Solna |
| ZIP/Postal code |
17165 |
| Country |
Sweden |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (1505)
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| Relations |
| BioProject |
PRJNA687490 |
| SRA |
SRP299088 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE163764_m1_patchseq_exon_counts.csv.gz |
15.9 Mb |
(ftp)(http) |
CSV |
| GSE163764_m1_patchseq_intron_counts.csv.gz |
11.4 Mb |
(ftp)(http) |
CSV |
| GSE163764_m1_patchseq_phys_temp_exon_counts.csv.gz |
2.5 Mb |
(ftp)(http) |
CSV |
| GSE163764_m1_patchseq_phys_temp_intron_counts.csv.gz |
1.5 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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