Researchers have published a spatiotemporal transcriptome of the human brain covering 1,340 tissue samples across 16 regions, mapping gene expression changes from embryonic development to late adulthood and offering new data for neurodevelopmental studies.
Understanding how the human brain develops from embryonic stages through to late adulthood requires looking beyond basic anatomy and examining the complex molecular activity unfolding across neural tissue. A massive dataset generated from 57 postmortem human brains offers a detailed look at this molecular landscape, capturing spatiotemporal dynamics across multiple regions and developmental periods. Past analyses profiling the developing human transcriptome relied on much more modest sample sizes, typically concentrating on limited time points or only a handful of specific brain regions.
Mapping the Human Brain Transcriptome Across 57 Donors
Researchers built this extensive transcriptome resource by analyzing 1,340 tissue samples sourced from the single or dual hemispheres of 57 deceased human brains. This collection spans from embryonic development to late adulthood, representing both males and females of multiple ethnicities. Researchers established a 15-period system to categorize human development and adulthood, capturing transient prenatal structures alongside immature and mature forms of 16 distinct brain regions.
The analyzed areas include the cerebellar cortex, mediodorsal nucleus of the thalamus, striatum, amygdala, hippocampus, and 11 distinct areas of the neocortex, which are referred to collectively as the region NCX. Alongside tissue collection, investigators genotyped donor DNA using an Illumina 2.5 million SNP chip and assessed copy number variations for all donors. The research specifically incorporated 39 cases where both hemispheres were available, drawing exclusively from clinically unremarkable donors exhibiting no evidence of large-scale genomic aberrations; the cohort spanned ages from 5.7 post-conceptual weeks to 82 years, including 31 males and 26 females, with a mean postmortem interval of 12.11±8.63 hours and a tissue pH of 6.45±0.34.
Prenatal Shifts and Regional Convergence in Gene Expression
Stringent criteria revealed that approximately 86% of protein-coding genes are expressed in the human brain. More than 90% of those expressed genes show differential regulation at the whole transcript or exon level across different regions, developmental periods, or both. The data shows that the majority of spatiotemporal differences occur before birth.
Following this early developmental activity, there is an increase in the similarity among regional transcriptomes during the postnatal lifespan. Genes were found to organize into functionally distinct co-expression networks, with sex differences present in gene expression and exon usage.
Implications for Neurodevelopmental Disorders
The research yields an open-access, detailed resource mapping the spatiotemporal gene expression of the human brain while shedding fresh light on the genetic underpinnings governing human neural development. Scientists can use these findings to map the developmental curves of genes tied to cell types, neurotransmitter systems, neurodevelopmental pathways, schizophrenia, and autism, as well as to identify links connecting single nucleotide polymorphisms with spatiotemporal expression patterns.
While the formation of molecularly distinct and intricate neural circuits grants humans remarkable cognitive and motor abilities, human-specific features of this process are likely to be important factors in the evolution of human specializations. However, this development may have also increased our susceptibility to certain psychiatric and neurological disorders. Sexual dimorphism significantly influences neural growth and operational capacity, serving as a known vulnerability element for conditions like autism spectrum disorders. By capturing these baseline developmental trajectories across diverse cohorts, the data offers researchers a clearer foundation for testing mechanisms related to brain evolution and disease.