Probabilistic cell typing enables fine mapping of closely related cell types in situ
File(s)
Author(s)
Type
Journal Article
Abstract
Understanding the function of a tissue requires knowing the spatial organization of its constituent cell types. In the cerebral cortex, single-cell RNA sequencing (scRNA-seq) has revealed the genome-wide expression patterns that define its many, closely related neuronal types, but cannot reveal their spatial arrangement. Here we introduce probabilistic cell typing by in situ sequencing (pciSeq), an approach that leverages previous scRNA-seq classification to identify cell types using multiplexed in situ RNA detection. We applied this method by mapping the inhibitory neurons of mouse hippocampal area CA1, for which ground truth is available from extensive previous work identifying their laminar organization. Our method identified these neuronal classes in a spatial arrangement matching ground truth, and further identified multiple classes of isocortical pyramidal cell in a pattern matching their known organization. This method will allow identifying the spatial organization of closely related cell types across the brain and other tissues.
Date Issued
2020-01-01
Date Acceptance
2019-10-08
Citation
Nature Methods, 2020, 17, pp.101-106
ISSN
1548-7091
Publisher
Nature Research
Start Page
101
End Page
106
Journal / Book Title
Nature Methods
Volume
17
Copyright Statement
© 2019 Springer Nature Limited. The final publication is available at Springer via https://doi.org/10.1038/s41592-019-0631-4
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31740815
PII: 10.1038/s41592-019-0631-4
Subjects
Science & Technology
Life Sciences & Biomedicine
Biochemical Research Methods
Biochemistry & Molecular Biology
SPATIAL-ORGANIZATION
SINGLE CELLS
ARCHITECTURE
Algorithms
Animals
CA1 Region, Hippocampal
Gene Expression Profiling
Male
Mice
Models, Statistical
Neocortex
Neurons
Pyramidal Cells
Sequence Analysis, RNA
Single-Cell Analysis
Pyramidal Cells
Neocortex
Neurons
Animals
Mice
Models, Statistical
Gene Expression Profiling
Sequence Analysis, RNA
Algorithms
Male
CA1 Region, Hippocampal
Single-Cell Analysis
Developmental Biology
06 Biological Sciences
10 Technology
11 Medical and Health Sciences
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2019-11-18