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Accelerated evolution of oligodendrocytes in the human brain
Edited by Pasko Rakic, Yale University, New Haven, CT, and approved October 21, 2019 (received for review May 8, 2019)

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Significance
Neurons have an important role in human brain evolution. However, the contribution of other brain cell types to human brain evolution has been largely unexplored. In this study, we take advantage of recent advances in transcriptomic profiling techniques to characterize 2 distinct cell types (neurons and oligodendrocytes) from the prefrontal cortex of human, chimpanzee, and rhesus macaque brain tissue. Our data reveal that oligodendrocytes have undergone an increased acceleration in the human lineage compared with neurons. Moreover, we find that human-specific genes in oligodendrocytes are enriched for genes associated with neuropsychiatric disorders, underscoring the importance of oligodendrocytes in both human brain evolution and cognitive diseases.
Abstract
Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell types follow similar or distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in neurons and oligodendrocytes and show that both cell types exhibit human-specific up-regulation. Moreover, oligodendrocytes have undergone more pronounced accelerated gene expression evolution in the human lineage compared to neurons. We highlighted human-specific coexpression networks with specific functions. Our data suggest that oligodendrocyte human-specific networks are enriched for alternative splicing and transcriptional regulation. Oligodendrocyte networks are also enriched for variants associated with schizophrenia and other neuropsychiatric disorders. Such enrichments were not found in neuronal networks. These results offer a glimpse into the molecular mechanisms of oligodendrocytes during evolution and how such mechanisms are associated with neuropsychiatric disorders.
Footnotes
↵1S.B., I.M., N.U., and K.T. contributed equally to this work.
- ↵2To whom correspondence may be addressed. Email: soojinyi{at}gatech.edu or genevieve.konopka{at}utsouthwestern.edu.
Author contributions: S.B., I.M., N.U., K.T., T.M.P., S.V.Y., and G.K. designed research; S.B., I.M., N.U., K.T., P.C., and C.D. performed research; C.A.T. contributed new reagents/analytic tools; S.B., I.M., N.U., K.T., T.M.P., S.V.Y., and G.K. analyzed data; and S.B., I.M., N.U., K.T., T.M.P., S.V.Y., and G.K. wrote the paper.
The authors declare no competing interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, https://www.ncbi.nlm.nih.gov/geo (human data, accession no. GSE107638; nonhuman primate data, accession no. GSE123936).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1907982116/-/DCSupplemental.
Published under the PNAS license.
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