Biology subjects

Lathia, K.

Publications and source records attributed to Lathia, K..

3 recordsLinked to original sources

bioRxiv2018

Conserved cell types with divergent features between human and mouse cortex

Elucidating the cellular architecture of the human neocortex is central to understanding our cognitive abilities and susceptibility to disease. Here we applied single nucleus RNA-sequencing to perform a comprehensive analysis of cell types in the middle temporal gyrus of human cerebral cortex. We identify a highly diverse set of excitatory and inhibitory neuronal types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to a similar mouse cortex single cell RNA-sequencing dataset revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of human cell type properties. Despite this general conservation, we also find extensive differences between homologous human and mouse cell types, including dramatic alterations in proportions, laminar distributions, gene expression, and morphology. These species-specific features emphasize the importance of directly studying human brain.

neuroscience↗

bioRxiv2017

Equivalent high-resolution identification of neuronal cell types with single-nucleus and single-cell RNA-sequencing

Transcriptional profiling of complex tissues by RNA-sequencing of single nuclei presents some advantages over whole cell analysis. It enables unbiased cellular coverage, lack of cell isolation-based transcriptional effects, and application to archived frozen specimens. Using a well-matched pair of single-nucleus RNA-seq (snRNA-seq) and single-cell RNA-seq (scRNA-seq) SMART-Seq v4 datasets from mouse visual cortex, we demonstrate that similarly high-resolution clustering of closely related neuronal types can be achieved with both methods if intronic sequences are included in nuclear RNA-seq analysis. More transcripts are detected in individual whole cells (~11,000 genes) than nuclei (~7,000 genes), but the majority of genes have similar detection across cells and nuclei. We estimate that the nuclear proportion of total cellular mRNA varies from 20% to over 50% for large and small pyramidal neurons, respectively. Together, these results illustrate the high information content of nuclear RNA for characterization of cellular diversity in brain tissues.

neuroscience↗

bioRxiv2017

Shared and distinct transcriptomic cell types across neocortical areas

Neocortex contains a multitude of cell types segregated into layers and functionally distinct regions. To investigate the diversity of cell types across the mouse neocortex, we analyzed 12,714 cells from the primary visual cortex (VISp), and 9,035 cells from the anterior lateral motor cortex (ALM) by deep single-cell RNA-sequencing (scRNA-seq), identifying 116 transcriptomic cell types. These two regions represent distant poles of the neocortex and perform distinct functions. We define 50 inhibitory transcriptomic cell types, all of which are shared across both cortical regions. In contrast, 49 of 52 excitatory transcriptomic types were found in either VISp or ALM, with only three present in both. By combining single cell RNA-seq and retrograde labeling, we demonstrate correspondence between excitatory transcriptomic types and their region-specific long-range target specificity. This study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct regions of the mouse cortex.

neuroscience↗