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Morphological, electrophysiological and transcriptomic profiling of single neurons using Patch-seq

ABSTRACT: The mammalian neocortex is a layered sheet of neural tissue that mediates complex cognitive processes including perception and cognition. Despite its importance, we still lack detailed knowledge of the cellular components of the neocortex. Integrating morphological, electrophysiological and molecular classification schemes into a common framework for defining cell types is challenging due to the limited scope of most single-cell analyses. Here, we developed a protocol for high-throughput electrophysiological and transcriptomic analysis of single neurons that combines whole-cell recordings and single-cell RNA-sequencing, which we call Patch-seq. Using this approach, we fully characterized the electrophysiological and molecular profiles of ~50 neocortical neurons, and show that gene expression patterns can be used to infer the morphological and physiological properties of individual neurons and their corresponding cell type. Our results shed light on the molecular underpinnings of neuronal diversity and demonstrate a path forward for comprehensive cell type characterization in the nervous system.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Mus musculus

SUBMITTER: Athanasia Palasantza 

PROVIDER: E-MTAB-4092 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Electrophysiological, transcriptomic and morphologic profiling of single neurons using Patch-seq.

Cadwell Cathryn R CR   Palasantza Athanasia A   Jiang Xiaolong X   Berens Philipp P   Deng Qiaolin Q   Yilmaz Marlene M   Reimer Jacob J   Shen Shan S   Bethge Matthias M   Tolias Kimberley F KF   Sandberg Rickard R   Tolias Andreas S AS  

Nature biotechnology 20151221 2

Despite the importance of the mammalian neocortex for complex cognitive processes, we still lack a comprehensive description of its cellular components. To improve the classification of neuronal cell types and the functional characterization of single neurons, we present Patch-seq, a method that combines whole-cell electrophysiological patch-clamp recordings, single-cell RNA-sequencing and morphological characterization. Following electrophysiological characterization, cell contents are aspirate  ...[more]

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