Vascular Patterning Dynamics

Pitulescu Lab

Deciphering organ-specific vascular patterning and artery formation in health and disease

It is fascinating that millions of cells and multiple distinct cell types are necessary to build an embryo. Nevertheless, to promote and sustain life, and ensure organism growth and functionality, sophisticated vascular networks form, extend, connect and remodel in tree-like structures in almost every organ of the living body. Endothelial cells, forming the inner lining of vessels, display different characteristics according to the vascular bed, functionality, or organ where they reside. Here, they adapt their behaviour to coordinate the assembly of the vascular network, by integrating organ-specific cues.

Rapidly progressing tissue engineering technology offers miniaturized three-dimensional models, promising for studying organ development and disease mechanisms, and paving the way for personalized medicine. However, vascularization is still one of the challenges of growing functional and complex "organs-in-a-dish", which relates to the fact that fundamental knowledge on mammalian organ vascularization is rather limited. In support of this, a major focus of our laboratory research is to decode the molecular mechanisms used by endothelial cells to make cell fate decisions, dynamically communicate with each other and the environment, to control vascular and tissue pattern generation during organogenesis and disease-induced repair conditions.

Regardless of the critical role of arteries and the severity of artery-associated pathologies that still pose considerable therapeutic difficulties, the cellular mechanisms controlling arterial fate specification and artery growth are largely unknown. We previously demonstrated that retinal arteries employ progeny of endothelial tip cells, specialized cells at the distal end of vascular plexus, for their growth (Pitulescu et al., Nat Cell Biol, 2017). Moreover, we identified a complex cascade of regulatory signaling pathways that coordinate different steps of artery growth (Stewen et al., Nat Commun, 2024). With our research, we aim to shed further light on the mechanisms of artery formation and maintenance in an organ-specific manner in health and disease.

Altogether, our research will enhance understanding of organ-specific vascular patterning and artery formation, with implications for the development of new strategies to improve vascularization in engineered tissues.

Image 1 (from left): Endothelial cells in 2D culture. Immunostained Human Umbilical Vein Endothelial Cells (HUVECs).Image 2: Intra-vessel heterogeneity. Single-cell RNA-seq of HUVECs (ref. Stewen et al., 2024)Image 3: Schematic of arteriovenous differentiation in postnatal mouse retina.Image 4: Genetically labeled ESM1+ tip cell-derived progeny incorporate into mouse retinal arteries but not into veins (ref. Pitulescu et al., 2017). — Image 1 (from left): Endothelial cells in 2D culture. Immunostained Human Umbilical Vein Endothelial Cells (HUVECs). Image 2: Intra-vessel heterogeneity. Single-cell RNA-seq of HUVECs (ref. Stewen et al., 2024) Image 3: Schematic of arteriovenous differentiation in postnatal mouse retina. Image 4: Genetically labeled ESM1+ tip cell-derived progeny incorporate into mouse retinal arteries but not into veins (ref. Pitulescu et al., 2017).

Image 1 (from left): Endothelial cells in 2D culture. Immunostained Human Umbilical Vein Endothelial Cells (HUVECs).
Image 2: Intra-vessel heterogeneity. Single-cell RNA-seq of HUVECs (ref. Stewen et al., 2024)
Image 3: Schematic of arteriovenous differentiation in postnatal mouse retina.
Image 4: Genetically labeled ESM1+ tip cell-derived progeny incorporate into mouse retinal arteries but not into veins (ref. Pitulescu et al., 2017).

Methodological and technical expertise

Advanced mouse genetics
High-resolution imaging techniques
In vitro models for molecular studies
Biochemical assays
Next-generation sequencing techniques