Single-cell multiomics decodes regulatory programs for mouse secondary palate development.

Area of Science:

• Developmental Biology
• Genomics
• Epigenetics

Background:

• Cleft palate is a common congenital birth defect.
• Gene regulatory disruptions during palatogenesis are implicated in its development.

Purpose of the Study:

• To comprehensively map epigenetic and transcriptional dynamics during mouse secondary palate development.
• To identify key transcription factors regulating palate formation.

Main Methods:

• Single-cell multiome sequencing (scMultiome) was performed on 36,154 cells from mouse secondary palate across embryonic days E12.5-E14.5.
• Chromatin accessibility and gene expression were profiled simultaneously within individual cells.
• Computational analysis, including trajectory inference and in silico perturbation, was used to identify regulatory relationships.

Main Results:

• Five differentiation trajectories from cranial neural crest-derived cells to distinct palate lineages were constructed.
• Lineage-determining transcription factors were characterized by linking open chromatin signals to gene expression.
• SHOX2 and MEOX2 were identified as critical regulators of anterior and posterior palate development, respectively.

Conclusions:

• This study provides a detailed atlas of epigenetic and transcriptional changes during palatogenesis.
• The findings offer valuable insights into the molecular mechanisms underlying palate development and identify potential therapeutic targets for cleft palate.
• The generated dataset serves as a crucial resource for future research on congenital birth defects.