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Gene expression patterns of the developing human face at single cell resolution reveal cell type contributions to normal facial variation and disease risk.

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Τίτλος: Gene expression patterns of the developing human face at single cell resolution reveal cell type contributions to normal facial variation and disease risk.
Συγγραφείς: Khouri-Farah N; Graduate Program in Genetics and Developmental Biology, UConn Health., Winchester EW; Graduate Program in Genetics and Developmental Biology, UConn Health., Schilder BM; Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, W12 0BZ, UK.; UK Dementia Research Institute at Imperial College London, London, W12 0BZ, UK., Robinson K; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA., Curtis SW; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA., Skene NG; Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, W12 0BZ, UK.; UK Dementia Research Institute at Imperial College London, London, W12 0BZ, UK., Leslie-Clarkson EJ; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA., Cotney J; Department of Surgery, Children's Hospital of Philadelphia, Philadelphia, PA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
Πηγή: BioRxiv : the preprint server for biology [bioRxiv] 2025 Feb 05. Date of Electronic Publication: 2025 Feb 05.
Τύπος έκδοσης: Journal Article; Preprint
Γλώσσα: English
Στοιχεία περιοδικού: Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet ISSN: 2692-8205 (Electronic) Linking ISSN: 26928205 NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE
Περίληψη: Craniofacial development gives rise to the complex structures of the face and involves the interplay of diverse cell types. Despite its importance, our understanding of human-specific craniofacial developmental mechanisms and their genetic underpinnings remains limited. Here, we present a comprehensive single-nucleus RNA sequencing (snRNA-seq) atlas of human craniofacial development from craniofacial tissues of 24 embryos that span six key time points during the embryonic period (4-8 post-conception weeks). This resource resolves the transcriptional dynamics of seven major cell types and uncovers distinct major cell types, including muscle progenitors and cranial neural crest cells (CNCCs), as well as dozens of subtypes of ectoderm and mesenchyme. Comparative analyses reveal substantial conservation of major cell types, alongside human biased differences in gene expression programs. CNCCs, which play a crucial role in craniofacial morphogenesis, exhibit the lowest marker gene conservation, underscoring their evolutionary plasticity. Spatial transcriptomics further localizes cell populations, providing a detailed view of their developmental roles and anatomical context. We also link these developmental processes to genetic variation, identifying cell type-specific enrichments for common variants associated with facial morphology and rare variants linked to orofacial clefts. Intriguingly, Neanderthal-introgressed sequences are enriched near genes with biased expression in cartilage and specialized ectodermal subtypes, suggesting their contribution to modern human craniofacial features. This atlas offers unprecedented insights into the cellular and genetic mechanisms shaping the human face, highlighting conserved and distinctly human aspects of craniofacial biology. Our findings illuminate the developmental origins of craniofacial disorders, the genetic basis of facial variation, and the evolutionary legacy of ancient hominins. This work provides a foundational resource for exploring craniofacial biology, with implications for developmental genetics, evolutionary biology, and clinical research into congenital anomalies.
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Grant Information: R03 DE027103 United States DE NIDCR NIH HHS; R01 DE030342 United States DE NIDCR NIH HHS; R03 DE028588 United States DE NIDCR NIH HHS; R01 DE028945 United States DE NIDCR NIH HHS; R35 GM119465 United States GM NIGMS NIH HHS; F30 DE031149 United States DE NIDCR NIH HHS
Entry Date(s): Date Created: 20250127 Latest Revision: 20250406
Update Code: 20260130
PubMed Central ID: PMC11761091
DOI: 10.1101/2025.01.18.633396
PMID: 39868299
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:2692-8205
DOI:10.1101/2025.01.18.633396