Analysis of candidate genes for cleft lip ± cleft palate using murine single-cell expression data

Area of Science:

• Developmental Biology
• Genetics
• Bioinformatics

Background:

• Cleft lip ± cleft palate (CL/P) is a frequent birth defect with complex genetic underpinnings.
• Identifying causal genes and functional networks for CL/P remains a significant challenge.
• Single-cell RNA sequencing (scRNA-seq) offers high-resolution gene expression analysis for developmental studies.

Purpose of the Study:

• To create a consolidated scRNA-seq resource for embryonic mouse craniofacial development.
• To investigate gene expression patterns of candidate genes associated with CL/P.
• To demonstrate the utility of scRNA-seq data in CL/P research.

Main Methods:

• Re-processed two existing scRNA-seq datasets from embryonic mice (E9.5-E13.5).
• Performed marker gene expression analysis to assess data resolution and identify cell types.
• Analyzed expression patterns of known CL/P candidate genes and their co-expression networks.

Main Results:

• Facial data at E11.5 provided high-resolution insights into craniofacial development.
• Identified specific co-expression networks for CL/P candidate genes (e.g., Irf6, Grhl3, Tfap2a) in different facial cell populations.
• Syndromic CL/P genes were expressed in more cell types than non-syndromic CL/P genes.

Conclusions:

• Aggregated scRNA-seq data serve as a valuable resource for craniofacial research.
• scRNA-seq effectively reveals cell-type-specific expression patterns of CL/P candidate genes.
• This approach enhances the investigation of genetic networks underlying CL/P.