Development of a single-cell mouse cortical gene expression pattern resource that identifies putative brain disorder subtypes

Transcriptional studies suggest that autism spectrum disorder (ASD), while encompassing a large number of distinct causal gene mutations, has some level of common molecular underpinning (e.g., Voineagu et al., Nature, 2011; Parikshak et al., Nature, 2016).

In a recent study, funded in part by a SFARI Research Award, Mark Zylka and colleagues have provided further insights into this potentially shared molecular pathology. Using single-cell RNA-seq data from wild-type mouse cerebral cortex at embryonic day 14.5 and at birth, the authors developed a catalog of cell-type specific gene expression patterns across distinct cortical layers.

They then went on to use this resource to demonstrate the existence of multiple ASD subtypes characterized by patterns of gene expression that highlight particular cell types and molecular pathways, broadly overlapping with synaptic transmission and transcriptional regulation. The successful identification of clinical subtypes of ciliopathies by mapping patterns of ciliopathy-associated gene expression holds out the prospect that similar analyses will be productive in ASD.

Researchers who are interested in exploring this resource can do so via a web-based platform built by the Zylka lab. Users can search for individual genes and explore cell type and age-specific expression patterns.

Identification of gene-expression-based disease subtypes. Hierarchical clustering of the expression values of genes linked to amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (ALZ), autism spectrum disorder (ASD), ciliopathies (CIL) and schizophrenia (SCZ) identified a number of putative subtypes within these disorders. Single-cell RNA-seq data from mouse cerebral cortex at embryonic day 14.5 (E) and at birth (P) formed the basis of these analyses. Image from Loo L. et al. (2019).


Single-cell transcriptomic analysis of mouse neocortical development.

Loo L., Simon J.M., Xing L., McCoy E.S., Niehaus J.K., Guo J., Anton E.S., Zylka M.

Nat. Commun. 10, 134 (January 10, 2019) PubMed

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