CD157⁺ vascular endothelial stem cells represent a conserved subpopulation with an angiogenic gene expression profile

Area of Science:

• Vascular Biology
• Cellular and Molecular Medicine

Background:

• Endothelial cells expressing CD157 (CD157⁺ ECs) are implicated in vascular regeneration and tissue maintenance.
• The precise molecular identity and function of CD157⁺ ECs remain incompletely understood.

Purpose of the Study:

• To define the molecular identity of CD157⁺ ECs in mouse and human tissues.
• To investigate the role of the NFAT pathway in CD157⁺ EC-mediated vascular network formation.
• To explore the functional characteristics and intercellular communication of human CD157⁺ ECs.

Main Methods:

• Comparative analysis of transcriptional profiles in mouse and human CD157⁺ ECs.
• Regulon and gene-regulatory network analysis, including NFAT pathway assessment.
• Integration of single-cell RNA sequencing (scRNA-seq) datasets from mouse and human.
• Isolation and functional assays (proliferation) of human CD157⁺ ECs.
• Cell-cell interaction analysis focusing on the CXCL12-CXCR7 axis.

Main Results:

• CD157⁺ ECs in mice and humans exhibit conserved transcriptional profiles enriched for angiogenesis-associated genes.
• NFAT pathway identified as a key regulator in vascular network formation.
• Human EC clusters resembling mouse CD157⁺ ECs were found in large vessel intima, expressing stem-like markers (BST1, PROCR, ABCG2).
• Human CD157⁺ ECs demonstrated superior proliferative capacity compared to CD157^- ECs.
• Active communication between CD157⁺ ECs and surrounding cells via the CXCL12-CXCR7 pathway was observed.

Conclusions:

• A conserved gene signature for CD157⁺ ECs has been identified, highlighting their role in vascular regeneration.
• These findings provide insights into the molecular mechanisms underlying vascular maintenance and repair.
• CD157⁺ ECs represent a promising target for therapeutic strategies aimed at promoting vascular health.