Dataset Information

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

ABSTRACT: Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferation. These genes comprised coherent processes, including cell-cycle progression and lysosomal signaling, which we determined to be human-derived by comparison with orangutan cells. Human-specific robustness to CDK2 and CCNE1 depletion persisted in neural progenitor cells and cerebral organoids, supporting the G1-phase length hypothesis as a potential evolutionary mechanism in human brain expansion. Our findings demonstrate that evolutionary changes in human cells reshaped the landscape of essential genes and establish a platform for systematically uncovering latent cellular and molecular differences between species.

SUBMITTER: She R

PROVIDER: S-EPMC10461406 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

She Richard R Fair Tyler T Schaefer Nathan K NK Saunders Reuben A RA Pavlovic Bryan J BJ Weissman Jonathan S JS Pollen Alex A AA

Cell 20230620 14

Comparative studies of great apes provide a window into our evolutionary past, but the extent and identity of cellular differences that emerged during hominin evolution remain largely unexplored. We established a comparative loss-of-function approach to evaluate whether human cells exhibit distinct genetic dependencies. By performing genome-wide CRISPR interference screens in human and chimpanzee pluripotent stem cells, we identified 75 genes with species-specific effects on cellular proliferati ...[more]

PMID: 37343560

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Project description:Chimpanzees (Pan troglodytes) are humans' closest living relatives, making them the most directly relevant comparison point for understanding human brain evolution. Zeroing in on the differences in brain connectivity between humans and chimpanzees can provide key insights into the specific evolutionary changes that might have occured along the human lineage. However, conducting comparisons of brain connectivity between humans and chimpanzees remains challenging, as cross-species brain atlases established within the same framework are currently lacking. Without the availability of cross-species brain atlases, the region-wise connectivity patterns between humans and chimpanzees cannot be directly compared. To address this gap, we built the first Chimpanzee Brainnetome Atlas (ChimpBNA) by following a well-established connectivity-based parcellation framework. Leveraging this new resource, we found substantial divergence in connectivity patterns across most association cortices, notably in the lateral temporal and dorsolateral prefrontal cortex between the two species. Intriguingly, these patterns significantly deviate from the patterns of cortical expansion observed in humans compared to chimpanzees. Additionally, we identified regions displaying connectional asymmetries that differed between species, likely resulting from evolutionary divergence. Genes associated with these divergent connectivities were found to be enriched in cell types crucial for cortical projection circuits and synapse formation. These genes exhibited more pronounced differences in expression patterns in regions with higher connectivity divergence, suggesting a potential foundation for brain connectivity evolution. Therefore, our study not only provides a fine-scale brain atlas of chimpanzees but also highlights the connectivity divergence between humans and chimpanzees in a more rigorous and comparative manner and suggests potential genetic correlates for the observed divergence in brain connectivity patterns between the two species. This can help us better understand the origins and development of uniquely human cognitive capabilities.

Dataset Information

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

Publications

Comparative landscape of genetic dependencies in human and chimpanzee stem cells.

Similar Datasets

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