Single-cell transcriptomic landscape of cardiac neural crest cell derivatives during development

Area of Science:

• Developmental Biology
• Cardiovascular Science
• Genomics

Background:

• Migratory cardiac neural crest cells (CNCCs) are crucial for cardiovascular development.
• Understanding CNCC derivatives is key to deciphering congenital heart anomalies.
• Detailed lineage and transcriptomic data of CNCC derivatives are lacking.

Purpose of the Study:

• To characterize the cell lineages, developmental chronology, and transcriptomic states of CNCC derivatives in the developing mouse heart.
• To identify and understand the transition of CNCC-derived mural cells (pericytes to microvascular smooth muscle cells).
• To explore the spatial distribution and regulatory dynamics of CNCC derivatives.

Main Methods:

• Single-cell transcriptomic sequencing of 34,131 CNCC-derived cells across eight developmental stages (E10.5-P7).
• Single-molecule fluorescence in situ hybridization (smFISH) for spatial distribution analysis.
• Computational reconstruction of differentiation paths and regulatory dynamics.

Main Results:

• Identified CNCC-derived mural cells, including pericytes and microvascular smooth muscle cells (mVSMCs).
• Characterized the transition from CNCC-derived pericytes to mVSMCs and identified key regulators.
• Provided evidence that many CNCC derivatives commit or differentiate prior to heart migration.
• Mapped the spatial distribution of critical CNCC-derived subpopulations.

Conclusions:

• This study offers novel insights into the cell lineages, developmental timing, and regulatory mechanisms of CNCC derivatives during heart development.
• The findings are essential for understanding the pathogenesis of CNCC-associated congenital anomalies.
• The data provide a comprehensive resource for future research on cardiac development and related disorders.