Cell type-specific genes show striking and distinct patterns of spatial expression in the mouse brain

Abstract

To characterize gene expression patterns in the regional subdivisions of the mammalian brain, we integrated spatial gene expression patterns from the Allen Brain Atlas for the adult mouse with panels of cell type-specific genes for neurons, astrocytes, and oligodendrocytes from previously published transcriptome profiling experiments. We found that the combined spatial expression patterns of 170 neuron-specific transcripts revealed strikingly clear and symmetrical signatures for most of the brain's major subdivisions. Moreover, the brain expression spatial signatures correspond to anatomical structures and may even reflect developmental ontogeny. Spatial expression profiles of astrocyte- and oligodendrocyte-specific genes also revealed regional differences; these defined fewer regions and were less distinct but still symmetrical in the coronal plane. Follow-up analysis suggested that region-based clustering of neuron-specific genes was related to (i) a combination of individual genes with restricted expression patterns, (ii) region-specific differences in the relative expression of functional groups of genes, and (iii) regional differences in neuronal density. Products from some of these neuron-specific genes are present in peripheral blood, raising the possibility that they could reflect the activities of disease- or injury-perturbed networks and collectively function as biomarkers for clinical disease diagnostics.

Fig. 1.

Transcriptionally distinct, spatially contiguous regions in the adult mouse brain revealed by clustering of neuron-, astrocyte-, and oligodendrocyte-specific genes. Expression data were assembled for sections through the center of the mouse brain. Reference atlases for regions visible on the coronal (A) and sagittal (B) planes. (C) k-Means clusters derived from the expression of neuron-, astrocyte-, or oligodendrocyte-specific genes (labeled N, A, and O, respectively) on the coronal plane (k = 3–20). (D) k-Means clustering based on the expression of these genes on the sagittal plane. Clustering of neuron-specific genes for larger numbers of clusters (k = 30–60), using expression on the coronal (E) and sagittal (F) planes.

Fig. 2.

Symmetry and transcriptional distinctiveness of k-means clusters derived from the spatial expression patterns of neuron-, astrocyte-, and oligodendrocyte-specific genes. (A) Heat maps depicting correlations between cluster assignments in the left vs. right hemisphere, relative to the distance of each point from the midline. Correlations are based on k-means clusters for neuron-, astrocyte-, or oligodendrocyte-specific genes at three representative numbers of clusters, k = 7, 10, and 18. (B) Probabilities (for k = 60 clusters) that adjacent neighbors of a patch lie in the same cluster. Probabilities for each cluster mapped to corresponding brain regions. Stars and grayed-out regions denote predominantly background clusters that could not be excluded a priori based on gene expression alone.

Fig. 3.