Exploring the human brain: spatial transcriptomics challenges and approaches in post-mortem analysis

Over the past century, studying the human brain has been one of the most complex and enduring biological challenges. Initial approaches, ranging from gross neural anatomy to cellular subtype organization, have significantly advanced our understanding of the intricate structure of the human brain. Recent innovations in spatial transcriptomic technologies offer high-resolution insights into mRNA expression at single-cell or even subcellular resolution. Developing a greater understanding of the spatial expression of genes in specific cell types in the human brain can provide additional insights into their functions and underlying mechanisms that influence neurological disease states. Whilst these tools have been highly successful in rodent and non-human primate brains, analysis of the human brain has several specific challenges. In this review, we first provide a comparison of spatial transcriptomics tools, followed by a summary of studies using these tools in human brains, and finally, discuss the challenges and opportunities associated. The guidelines should enable researchers to address the challenges of using new spatial transcriptomics technologies to analyse complex organs like the human brain.