Single-cell-resolution transcriptome map of human, chimpanzee, bonobo, and macaque brains

Abstract

Identification of gene expression traits unique to the human brain sheds light on the mechanisms of human cognition. Here we searched for gene expression traits separating humans from other primates by analyzing 88,047 cell nuclei and 422 tissue samples representing 33 brain regions of humans, chimpanzees, bonobos, and macaques. We show that gene expression evolves rapidly within cell types, with more than two-thirds of cell type-specific differences not detected using conventional RNA sequencing of tissue samples. Neurons tend to evolve faster in all hominids, but non-neuronal cell types, such as astrocytes and oligodendrocyte progenitors, show more differences on the human lineage, including alterations of spatial distribution across neocortical layers.

Single-cell analysis of human retina identifies evolutionarily conserved and species-specific mechanisms controlling development

“…In human corticogenesis, it has been hypothesized that coordinated changes in regulatory domains of co-expressed genes drive cortical evolution (Reilly et al, 2015). This is further highlighted by large transcriptional differences observed in brain cell type evolution across the primate lineage, despite little sequence divergence in protein coding genes (Khrameeva et al, 2019). Hence, it is possible that the divergent expression patterns of conserved genes across human and mouse retinal development corresponds to changes in the use and/or sequence of transcriptional regulatory elements.…”

Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum

“…79 We converted rodent genes to rhesus macaque genes by BioMart Ensemble, keeping one-to-one orthologs only. 80,81 For MSN analysis, we isolated the clusters that were enriched with well-known marker MSN genes including PPP1R1B, BCL11B, and PDE1B. In order to balance the number of nuclei per animal, we randomly sampled MSN and MSN-like nuclei from monkey P to levels of monkey F (7,387 nuclei).…”

“…We repeated these 10,001 times and used within group and between group variance ratio to determine a p value. To compare the cell types between monkey and mouse MSNs, we first generated an orthologous gene list between mouse and rhesus macaque from BioMart Ensemble with one-to-one orthologous genes 80,81 used for downstream analysis. We integrated our MSNs and MSN-like nuclei from the two monkeys with MSN types in Stanley et al 15 based on the homologous genes using the Seurat integration method as above for the two animals.…”

Unraveling patterns of disrupted gene expression across a complex tissue

“…For example, laser capture microdissection provides a means to rapidly and precisely isolate cellular populations from complex tissues (Emmert-Buck et al 1996), albeit with the added requirement of highly specialized instrumentation. It is common in behavioral research to dissect out major regions of the brain rather than sampling the whole brain (Khrameeva et al 2020;Sato et al 2020). Thus, a chemical or mechanical approach to partitioning complex tissues can provide researchers with a way of minimizing the negative effects associated with bulk RNASeq in their own studies.…”