A high-resolution transcriptomic and spatial atlas of cell types in the whole mouse brain

The mammalian brain consists of millions to billions of cells that are organized
into many cell types with specific spatial distribution patterns and structural and
functional properties1–3. Here we report a comprehensive and high-resolution
transcriptomic and spatial cell-type atlas for the whole adult mouse brain. The
cell-type atlas was created by combining a single-cell RNA-sequencing (scRNA-seq)
dataset of around 7 million cells profiled (approximately 4.0 million cells passing
quality control), and a spatial transcriptomic dataset of approximately 4.3 million
cells using multiplexed error-robust fluorescence in situ hybridization (MERFISH).
The atlas is hierarchically organized into 4 nested levels of classification: 34 classes,
338 subclasses, 1,201 supertypes and 5,322 clusters. We present an online platform,
Allen Brain Cell Atlas, to visualize the mouse whole-brain cell-type atlas along with the
single-cell RNA-sequencing and MERFISH datasets. We systematically analysed the
neuronal and non-neuronal cell types across the brain and identified a high degree of
correspondence between transcriptomic identity and spatial specificity for each cell
type. The results reveal unique features of cell-type organization in different brain
regions—in particular, a dichotomy between the dorsal and ventral parts of the brain.
The dorsal part contains relatively fewer yet highly divergent neuronal types, whereas
the ventral part contains more numerous neuronal types that are more closely related
to each other. Our study also uncovered extraordinary diversity and heterogeneity
in neurotransmitter and neuropeptide expression and co-expression patterns in
different cell types. Finally, we found that transcription factors are major determinants
of cell-type classification and identified a combinatorial transcription factor code that
defines cell types across all parts of the brain. The whole mouse brain transcriptomic
and spatial cell-type atlas establishes a benchmark reference atlas and a foundational
resource for integrative investigations of cellular and circuit function, development
and evolution of the mammalian brain.