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Neuron. 2017 May 17;94(4):752-758.e1. doi: 10.1016/j.neuron.2017.05.008.

seqFISH Accurately Detects Transcripts in Single Cells and Reveals Robust Spatial Organization in the Hippocampus.

Author information

1
Division of Chemistry and Chemical 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 Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
3
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: lcai@caltech.edu.

Abstract

We recently applied multiplexed seqFISH to profile expressions of hundreds of genes at the single-cell level in situ (Shah et al., 2016) and provided a map of spatial heterogeneity within each subregion, reconciling previously contradictory descriptions of CA1 at lower spatial resolutions. The accompanying Matters Arising paper from Cembrowski and Spruston questions the spatial organization described for CA1 and raise concerns that the results were determined only by high expression, non-barcoded genes. In response, we show that the same robust spatial structure is observed when only lower average abundance genes measured by barcoded seqFISH are used. In fact, many genes with low average abundance are informative of cell states because they can be expressed strongly in specific subpopulation of cells. Our discussion highlights the importance of single-cell in situ analysis in resolving cellular and spatial heterogeneities otherwise lost in population-averaged measurements. This Matters Arising Response paper addresses the Cembrowski and Spruston (2017) Matters Arising paper, published concurrently in this issue of Neuron.

PMID:
28521130
DOI:
10.1016/j.neuron.2017.05.008
[Indexed for MEDLINE]
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