Comparative transcriptomics in human and mouse

The mouse is the most widely used model organism to study human disease, but often mouse biology cannot be extrapolated to humans. A deep comparison of mouse and human physiology at the molecular level is essential for understanding under which circumstances the mouse can be a suitable model of human biology and for creating better mouse models. Advances in next-generation sequencing technologies fostered genome-wide annotation of functional DNA elements, enabling extensive comparison of the human and mouse genomes.At the transcriptional level, human and mouse gene expression profiles are conserved overall, although the degree of conservation varies depending on the tissues and the genes that are compared. Therefore, the question of whether the human and mouse transcriptomes cluster preferentially by tissue or organ or by species does not have an answer overall, and it depends specifically on the genes being considered.Conservation of expression is not a direct consequence of conservation in regulatory sequences, including promoters and enhancers. Although gene regulatory networks are preserved overall between human and mouse, transcription binding sites are often not conserved.Inter-individual genetic variation can affect human gene expression, but such variation cannot be modelled in inbred strains of laboratory mice because their genetic variation is small compared to the human population. An expansion of the current studies on the relationship between genetic variation and gene expression in outbred mice might provide helpful insights to understand the same relationship in humans.Emerging technologies — such single-cell genomics and single-cell spatial transcriptomics — and time series experiments will improve the annotation of human and mouse genomes, refine the current definitions of homologous cell types and homologous (molecular) phenotypes, and ultimately help scientists to identify which mouse models are the most appropriate to address a given biological question.