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Neuron. 2016 Oct 19;92(2):342-357. doi: 10.1016/j.neuron.2016.10.001.

In Situ Transcription Profiling of Single Cells Reveals Spatial Organization of Cells in the Mouse Hippocampus.

Author information

1
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; UCLA-Caltech Medical Scientist Training Program, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
3
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
4
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: lcai@caltech.edu.

Abstract

Identifying the spatial organization of tissues at cellular resolution from single-cell gene expression profiles is essential to understanding biological systems. Using an in situ 3D multiplexed imaging method, seqFISH, we identify unique transcriptional states by quantifying and clustering up to 249 genes in 16,958 cells to examine whether the hippocampus is organized into transcriptionally distinct subregions. We identified distinct layers in the dentate gyrus corresponding to the granule cell layer and the subgranular zone and, contrary to previous reports, discovered that distinct subregions within the CA1 and CA3 are composed of unique combinations of cells in different transcriptional states. In addition, we found that the dorsal CA1 is relatively homogeneous at the single cell level, while ventral CA1 is highly heterogeneous. These structures and patterns are observed using different mice and different sets of genes. Together, these results demonstrate the power of seqFISH in transcriptional profiling of complex tissues.

PMID:
27764670
PMCID:
PMC5087994
DOI:
10.1016/j.neuron.2016.10.001
[Indexed for MEDLINE]
Free PMC Article

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