Whole-brain comparison of rodent and human brains using spatial transcriptomics
Abstract
The ever-increasing use of mouse models in preclinical neuroscience research calls for an improvement in the methods used to translate findings between mouse and human brains. Previously we showed that the brains of primates can be compared in a direct quantitative manner using a common reference space built from white matter tractography data (Rogier B. Mars et al., 2018b). Here we extend the common space approach to evaluate the similarity of mouse and human brain regions using openly accessible brain-wide transcriptomic data sets. We show that mouse-human homologous genes capture broad patterns of neuroanatomical organization, but that the resolution of cross-species correspondences can be improved using a novel supervised machine learning approach. Using this method, we demonstrate that sensorimotor subdivisions of the neocortex exhibit greater similarity between species, compared with supramodal subdivisions, and that mouse isocortical regions separate into sensorimotor and supramodal clusters based on their similarity to human cortical regions. We also find that mouse and human striatal regions are strongly conserved, with the mouse caudoputamen exhibiting an equal degree of similarity to both the human caudate and putamen.
Data availability
The Allen Mouse Brain Atlas and Allen Human Brain Atlas data sets are openly accessible and can be downloaded from the Allen Institute's API (http://api.brain-map.org). All of the code and additional data needed to generate this analysis, including figures and manuscript, is accessible at https://github.com/abeaucha/MouseHumanTranscriptomicSimilarity/
Article and author information
Author details
Funding
Canadian Institutes of Health Research (Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-165737))
- Antoine Beauchamp
Wellcome Trust (203139/Z/16/Z)
- Rogier B Mars
- Jason P Lerch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 5,731
- views
-
- 587
- downloads
-
- 48
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Evolutionary Biology
Studying the fecal microbiota of wild baboons helps provide new insight into the factors that influence biological aging.
-
- Evolutionary Biology
The majority of highly polymorphic genes are related to immune functions and with over 100 alleles within a population, genes of the major histocompatibility complex (MHC) are the most polymorphic loci in vertebrates. How such extraordinary polymorphism arose and is maintained is controversial. One possibility is heterozygote advantage (HA), which can in principle maintain any number of alleles, but biologically explicit models based on this mechanism have so far failed to reliably predict the coexistence of significantly more than ten alleles. We here present an eco-evolutionary model showing that evolution can result in the emergence and maintenance of more than 100 alleles under HA if the following two assumptions are fulfilled: first, pathogens are lethal in the absence of an appropriate immune defence; second, the effect of pathogens depends on host condition, with hosts in poorer condition being affected more strongly. Thus, our results show that HA can be a more potent force in explaining the extraordinary polymorphism found at MHC loci than currently recognized.