Single-cell transcriptome analysis reveals characteristic transcription factors in polydactyly

Area of Science:

• Developmental Biology
• Genetics
• Molecular Biology

Background:

• Multiple-digit malformations, such as polydactyly, represent complex congenital conditions.
• Understanding the molecular mechanisms underlying these malformations is crucial for identifying biomarkers and therapeutic targets.

Purpose of the Study:

• To identify multiple-digit malformations as potential biomarkers and therapeutic targets.
• To elucidate the molecular pathways involved in polydactyly development.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) data from polydactyly samples were analyzed.
• Fibroblasts and keratinocytes were profiled to identify cellular subpopulations.
• Transcriptional regulatory networks and regulon functionality were investigated.

Main Results:

• Analysis of 11,806 single cells revealed significant associations between regulons and cell function in polydactyly.
• HOX family members and GLI2 transcription factors (e.g., HOXD13, MSX2, LHX2) were implicated in fibroblast development during polydactyly.
• HES2 and GLIS1 were identified as key factors in keratinocyte formation and development.

Conclusions:

• The study highlights the significant role of transcription factors, particularly HOXD13, MSX2, and LHX2, in polydactyly.
• These findings provide insights into the genetic basis of polydactyly and suggest potential therapeutic avenues.