Lineage Tracing Identifies Dynamic Contribution of Endothelial Cells to Cardiac Valve Mesenchyme During Development

Xiaojie Yang1, Furong Lu1

  • 1College of Life Sciences and Technology, Jinan University, Guangzhou, China.

Insights

Understanding heart valve development is key to treating congenital heart disease. This study traces endothelial cells, revealing their dynamic contribution to valve layers during development, crucial for understanding valve remodeling.

Area of Science:

  • Cardiovascular Biology
  • Developmental Biology
  • Genetics

Background:

  • Heart valve disease contributes significantly to global morbidity and mortality.
  • The precise pathogenesis of heart valve disease remains unclear, with emerging evidence pointing to genetic and developmental origins.
  • Understanding heart valve development is critical for diagnosing, preventing, and treating congenital heart disease.

Purpose of the Study:

  • To investigate the dynamic contribution of endocardial cushion-derived endothelial cells to heart valve layers during development.
  • To elucidate the cellular dynamics within the heart valve mesenchymal population.
  • To enhance understanding of endocardial cell roles in valve remodeling.

Main Methods:

  • Utilized the Cdh5-CreER;R26R-tdTomato mouse line for lineage tracing.
  • Tracked endocardial cushion-derived endothelial cells throughout valve development.
  • Analyzed the cellular contribution to different valve layers.

Main Results:

  • Successfully traced the contribution of endocardial cells to specific valve layers.
  • Visualized the dynamic changes in cell localization and proportion within the valve mesenchyme.
  • Provided insights into the developmental trajectory of endothelial cells in valve formation.

Conclusions:

  • Endocardial cells play a dynamic and crucial role in heart valve development and remodeling.
  • Lineage tracing provides a precise method for understanding cellular contributions to valve formation.
  • Further research into these developmental mechanisms can inform therapeutic strategies for heart valve diseases.

Related Concept Videos

Development of Blood Vessels01:07

Development of Blood Vessels

The development of the vascular system in a fetus is a complex and intricate process that begins as early as 15 to 16 days post-conception. This process starts outside the embryo, specifically in the mesoderm of the yolk sac, chorion, and connecting stalk. Approximately two days later, the formation of blood vessels occurs within the embryo itself.
The initial formation of this system is facilitated by the small amount of yolk present in the ovum and yolk sac. Blood vessels originate from...
601
Development of the Heart01:27

Development of the Heart

The development of the human heart, a crucial organ, commences from the mesoderm on the 18th or 19th day after fertilization. This process initiates in the cardiogenic area, a group of mesodermal cells at the embryo's head end, which evolves into elongated strands known as cardiogenic cords. These cords undergo a transformation to form hollow-centered endocardial tubes.
As the embryo undergoes lateral folding, these paired tubes approach each other, merging into a single primitive heart...
980
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
Overview of the Vascular System01:20

Overview of the Vascular System

The vascular system comprises an extensive network of arteries, capillaries, and veins. The vascular system can be broadly divided into the blood and lymphatic systems. Typically, blood vessels can be categorized into three histological regions: tunica intima, tunica media, and tunica adventitia. The tunica intima consists of a single layer of endothelial cells attached to the basal lamina. Underlying the basal lamina is a connective tissue layer and an elastic lamina that gives stability and...
2.8K
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
5.5K
Heart Valves01:16

Heart Valves

The human heart is a complex organ with an intricate system of valves that regulate blood flow. There are two main types of valves: atrioventricular (AV) valves and semilunar valves.
The AV valves prevent the backflow of blood from the ventricles to the atria during ventricular contraction. These valves function with the assistance of the chordae tendineae and papillary muscles. When the ventricles are relaxed, the chordae tendineae are slack, allowing blood to flow from the atria into the...
4.8K