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. 2025 Mar 20;188(6):1504-1523.e27.
doi: 10.1016/j.cell.2025.01.007. Epub 2025 Jan 30.

Resolving the three-dimensional interactome of human accelerated regions during human and chimpanzee neurodevelopment

Atreyo Pal  1 , Mark A Noble  1 , Matheo Morales  1 , Richik Pal  2 , Marybeth Baumgartner  1 , Je Won Yang  1 , Kristina M Yim  1 , Severin Uebbing  1 , James P Noonan  3
Affiliations

Resolving the three-dimensional interactome of human accelerated regions during human and chimpanzee neurodevelopment

Atreyo Pal et al. Cell. .

Erratum in

Abstract

Human accelerated regions (HARs) have been implicated in human brain evolution. However, insight into the genes and pathways they control is lacking, hindering the understanding of their function. Here, we identify 2,963 conserved gene targets for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs). Conserved gene targets are enriched for neurodevelopmental functions and are overrepresented among differentially expressed genes (DEGs) identified in human NSCs (hNSCs) and chimpanzee NSCs (cNSCs) as well as in human versus non-human primate brains. Species-specific gene targets do not converge on any function and are not enriched among DEGs. HAR targets also show cell-type-specific expression in the human fetal brain, including in outer radial glia, which are linked to cortical expansion. Our findings support that HARs influence brain evolution by altering the expression of ancestral gene targets shared between human and chimpanzee rather than by gaining new targets in human and facilitate hypothesis-directed studies of HAR biology.

Keywords: human accelerated regions; human brain evolution; human gain enhancers; neurodevelopment; outer radial glia.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

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