Brain

The brain and spinal cord form the central nervous system, with anatomically specialized regions involved in sensory processing, movement, cognition and physiological regulation. Although the overall organization of the central nervous system is conserved across mammals, substantial differences in brain size, cortical folding and regional specialization influence both anatomy and tissue sampling. In particular, humans, macaques and pigs have a folded cerebral cortex with distinct gyri and sulci, whereas the rodent cortex is largely smooth, making direct comparisons between cortical regions more challenging.

Sampling covers multiple cortical and subcortical regions, the cerebellum, brainstem and parts of the spinal cord. The macaque has the most anatomically subdivided cortical sampling, including individual frontal, temporal, parietal and occipital gyri, while pig cortex is sampled by broader functional regions. Rat and mouse cortex are represented by fewer, broader dissections, reflecting their smaller brain size and different cortical organization. The sampling strategy also differs in anatomical resolution: human brain data in the HPA Brain Resource and parts of the macaque dataset are based on small, anatomically defined micropunches, whereas rat and mouse samples often represent entire subregions. Consequently, the smaller rodent brain is represented by relatively comprehensive regional sampling, while individual samples may contain a broader mixture of cell populations.

Shared regions such as the amygdala, thalamus, cerebellum, pons and medulla support cross-species comparisons, although anatomical boundaries and dissection labels are not always equivalent. Some specialized samples, such as the choroid plexus, corpus callosum and dorsal root ganglion, are available only in subsets of species, and missing regions should not be interpreted as anatomically absent. Importantly, the most relevant human reference for regional brain comparisons is the micropunch-based RNA dataset in the HPA Brain Resource, rather than the limited representation in the HPA Tissue Resource.

Figure 1. Tissue sample overview and hierarchy of regions representing the brain

Comparative transcriptomics of the mammalian endocrine tissues

The transcriptomic data is used to identify genes with elevated expression in individual tissues or groups of tissues, classified into three categories:

Tissue enriched: Genes with elevated expression in a single tissue compared with all other tissues.
Group enriched: Genes with elevated expression in a limited group of tissues compared with the remaining tissues.
Tissue enhanced: Genes with elevated expression in one or more tissues compared with the average expression across tissues (gap ratio ≥2)

Tissue specificity is evaluated at two levels: first, within each species using all available tissue types, and second, using only tissues that can be directly compared between the species and human. This distinction makes it possible to explore both tissue-specific expression within each species and the conservation of expression patterns across evolution.

The results can be explored for individual genes on the gene summary pages or searched to identify genes with specific expression patterns. To assess evolutionary conservation, pairwise overlap analysis compares each species individually with human, identifying genes that share the same tissue specificity classification in corresponding tissues and quantifying the extent of overlap between species.

Tissue	Species	Elevated	Human elevated overlap
Tissue	Species	Elevated	Complete overlap	Partial overlap
Brain	Macaque	1979	661	582
	Mouse	1991	533	687
	Rat	1845	548	636
	Pig	1609	536	589
Choroid plexus	Rat	169	10	59
Choroid plexus	Pig	202	15	61

Species coverage

Macaque (50 subregions)

olfactory bulb; superior frontal gyrus; middle frontal gyrus; inferior frontal gyrus; gyrus rectus; orbital gyrus; precentral gyrus; postcentral gyrus; superior parietal lobule; supramarginal gyrus; angular gyrus; superior temporal gyrus; middle temporal gyrus; inferior temporal gyrus; fusiform gyrus; posterior parahippocampal gyrus; anterior cingulate gyrus; posterior cingulate cortex; insular cortex; claustrum; cuneus; annectant gyrus; occipital gyrus; inferior occipital gyrus; entorhinal cortex; hippocampal formation; subiculum; amygdala; septum; globus pallidus; caudate nucleus; putamen; thalamus; geniculate nucleus; lateral thalamic nuclei; posterior thalamus; habenula; hypothalamus, anterior; hypothalamus, posterior; preoptic area; midbrain; substantia nigra; superior colliculi; cerebellum; pons; medulla oblongata; dorsal root ganglion; dorsal spinal cord; ventral spinal cord; white matter.

Mouse (18 subregions)

olfactory bulb; motor and prefrontal cortex; somatosensory cortex; retrosplenial and cingulate cortex; visual cortex; entorhinal cortex; hippocampal formation; amygdala; septum; ventral forebrain; caudate putamen; thalamus; hypothalamus; midbrain; cerebellum; pons; medulla oblongata; spinal cord.

Rat (21 subregions)

olfactory bulb; frontal cortex; somatosensory cortex; retrosplenial and cingulate cortex; occipital cortex; entorhinal cortex; ventral hippocampus; amygdala; ventral forebrain; septal area; caudate putamen; thalamus; hypothalamus; midbrain; cerebellum; pons; medulla oblongata; dorsal root ganglion; ventral spinal cord; choroid plexus; corpus callosum.

Pig (31 subregions)

olfactory bulb; prefrontal cortex; motor cortex; somatosensory cortex; temporal cortex; cingulate cortex; retrosplenial cortex; insular cortex; occipital cortex; entorhinal cortex; subiculum; dorsal hippocampus; ventral hippocampus; amygdala; septum; ventral pallidum; caudate nucleus; putamen; thalamus; hypothalamus; midbrain; substantia nigra; superior colliculi; periaqueductal gray; cerebellum; pons; medulla oblongata; dorsal spinal cord; ventral spinal cord; choroid plexus; corpus callosum.