Single-Cell Transcriptomics and Lineage Tracing Unveil Parallels in Lymphatic Muscle and Venous Smooth Muscle...

Area of Science:

• Vascular Biology
• Developmental Biology
• Cellular Biology

Background:

• Lymphatic muscle cells (LMCs) are crucial for lymphatic vessel contraction, but their cellular and molecular underpinnings remain poorly understood.
• Dysfunctional LMCs are implicated in primary and secondary lymphedema, highlighting the need for therapeutic targets.

Purpose of the Study:

• To investigate the cellular and molecular basis of lymphatic muscle cell (LMC) characteristics.
• To understand the origins and functional properties of LMCs in relation to vascular smooth muscle cells (SMCs).

Main Methods:

• Single-cell RNA sequencing to compare LMC and SMC transcriptomes.
• Genetic lineage tracing to determine LMC developmental origins.
• Immunostaining and intravital imaging to assess lymphatic and blood vessel function.

Main Results:

• LMCs and venous SMCs share overlapping transcriptomic profiles, distinct from arteriole SMCs.
• LMCs and hind limb blood vessels exhibit pulsatile contractility regulated by calcium channels.
• Lineage tracing revealed LMCs originate from WT1+ mesodermal progenitors, not cardiomyocyte or neural crest sources.

Conclusions:

• Lymphatic muscle cells (LMCs) and venous smooth muscle cells (SMCs) arise from a common mesodermal progenitor.
• Shared gene expression programs contribute to the contractile functions of both LMCs and venous SMCs.
• WT1+ mesodermal progenitors are critical for LMC development and lymphatic vessel contractility.