Resolving the design principles that control post-natal vascular growth and scaling

Area of Science:

• Developmental Biology
• Biophysics
• Cellular Dynamics

Background:

• Postnatal tissue growth involves unique cellular dynamics and cell sources for each organ.
• Organ enlargement follows specific growth principles, but the mechanisms governing aortic growth are not fully understood.

Purpose of the Study:

• To elucidate the principles of aortic enlargement and its scaling with the vertebral column.
• To investigate the cellular dynamics, proliferation patterns, and metabolic changes during aortic growth.
• To understand the role of endothelial cell extrusion in maintaining aortic size homeostasis.

Main Methods:

• Multiscale experimental and computational approaches.
• Single-cell RNA sequencing.
• Mathematical modeling and genetic manipulation (achondroplasia model).

Main Results:

• Aortic enlargement follows distinct growth principles, scaling with the vertebral column.
• Expansion occurs in two coordinated, stochastic proliferation waves aligned with blood flow, with rapid cell cycles (as short as 6 h) in the first wave.
• Increased fatty acid metabolism accompanies cell enlargement, and endothelial cell extrusion is essential for size homeostasis by compensating for proliferation excess.

Conclusions:

• Aortic growth relies on the proliferation of resident differentiated cells.
• Endothelial cell extrusion is a key mechanism for maintaining aortic size during development.
• The study provides a blueprint for orchestrating aortic growth principles, highlighting the importance of cell extrusion in conditions like achondroplasia.