ArticleNature genetics2021
Human-chimpanzee fused cells reveal cis-regulatory divergence underlying skeletal evolution.
Article in Nature genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 89 citations in OpenAlex.
- Atlas of cell types and regulatory elements underlying human facial diversity.Nature genetics · 2026Article
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- Developmental signaling reveals functionally enriched human-specific gene regulation in telencephalic progenitors.bioRxiv : the preprint server for biology · 2026Article
- CellBouncer, a unified toolkit for single-cell demultiplexing and ambient RNA analysis, reveals hominid mitochondrial incompatibilities.Cell genomics · 2026Article
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- Adaptive loss of function accelerated the evolution of ancient and modern human cognition.bioRxiv : the preprint server for biology · 2026Article
- Beyond the mean: genetic control of gene expression fidelity and dispersion.bioRxiv : the preprint server for biology · 2026Article
- Species-specific chromatin architecture and neurogenesis mediated by a human enhancer.Cell stem cell · 2026Article
- In silico genome transplants and the cis-regulatory basis of biodiversity.Trends in genetics : TIG · 2026Review
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- Hominoid-specific transposable elements reshaped neural crest migration in craniofacial development.Molecular systems biology · 2025Article
- Shaping the Neocortex: Radial Glia and Astrocytes in Development and Evolution.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Harnessing fusion of genome-edited human stem cells to rapidly screen for novel protein functions in vivo.Molecular biology of the cell · 2025Article
- Read mismapping from segmental duplications drives spuriousbioRxiv : the preprint server for biology · 2025Article
- RoAM: computational reconstruction of ancient methylomes and identification of differentially methylated regions.Genome biology · 2025Article
- A General Principle of Neuronal Evolution Reveals a Human-Accelerated Neuron Type Potentially Underlying the High Prevalence of Autism in Humans.Molecular biology and evolution · 2025Article
- Article
- The regulatory architecture of gene expression variation in Caenorhabditis elegans revealed by multi-strain allele-specific analysis.Genetics · 2025Article
- Genetic Architecture of Immune Cell DNA Methylation in the Rhesus Macaque.Molecular ecology · 2025Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Gene regulatory divergence is thought to play a central role in determining human-specific traits. However, our ability to link divergent regulation to divergent phenotypes is limited. Here, we utilized human-chimpanzee hybrid induced pluripotent stem cells to study gene expression separating these species. The tetraploid hybrid cells allowed us to separate cis- from trans-regulatory effects, and to control for nongenetic confounding factors. We differentiated these cells into cranial neural crest cells, the primary cell type giving rise to the face. We discovered evidence of lineage-specific selection on the hedgehog signaling pathway, including a human-specific sixfold down-regulation of EVC2 (LIMBIN), a key hedgehog gene. Inducing a similar down-regulation of EVC2 substantially reduced hedgehog signaling output. Mice and humans lacking functional EVC2 show striking phenotypic parallels to human-chimpanzee craniofacial differences, suggesting that the regulatory divergence of hedgehog signaling may have contributed to the unique craniofacial morphology of humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.