Endothelialization and altered hematopoiesis by persistent Etv2 expression in mice

Area of Science:

• Developmental Biology
• Hematopoiesis
• Vascular Biology

Background:

• Etv2 is a master regulator of hematopoietic and endothelial cell development.
• Etv2 expression is transient during normal cell differentiation.
• The role of transient Etv2 expression in development is understudied.

Purpose of the Study:

• To investigate the necessity of transient Etv2 expression for normal development and cell differentiation.
• To determine the effects of constitutive Etv2 expression on various cell lineages.

Main Methods:

• Generated transgenic mice with Cre-activatable ROSA26 locus for constitutive Etv2 expression.
• Utilized Tie-2 Cre and Vav-iCre transgenes to target endothelial/hematopoietic and adult hematopoietic lineages, respectively.
• Analyzed developmental and cellular phenotypes in hematopoietic, endothelial, somite, and neuronal lineages.

Main Results:

• Constitutive Etv2 expression primarily affected hematopoietic and endothelial lineages, causing abnormal yolk sac vasculature.
• Etv2 overexpression led to prolonged vascular endothelial cadherin expression and impaired B lymphopoiesis.
• In adult hematopoietic cells, constitutive Etv2 conferred an endothelial phenotype, suppressed hematopoiesis, and severely impacted erythropoiesis.

Conclusions:

• Constitutive Etv2 expression perturbs vascular development and hematopoiesis.
• Etv2's role in promoting hematopoiesis and vasculogenesis requires tight temporal regulation.
• Transient Etv2 expression is essential for normal vascular and hematopoietic development.