Picture of the week

Here you can find amazing images from IGP researchers.

Colored-coded clones to study vascular malformations

By Hans Schoofs
2 July, 2020

Confocal microscope image of mouse ear skin showing clonally labelled endothelial cells (nuclei are stochastically labeled green, red or cyan) in blood vessels (gray) or lymphatic vessels (yellow).

Confocal microscope image of mouse ear skin showing cells in vessels

Background

Vascular anomalies are a group of rare diseases whereby the endothelial cells lining blood and lymphatic vessels develop or grow abnormally. The often rapid and uncontrolled growth of these vessels can cause disfigurement in affected patients but can also functionally impair the patients blood flow, reducing quality of live. To date, these patients are mostly treated by resecting the affected tissue, a surgical procedure which often needs to be repeated.

In the past few years, research from various groups have shown that these vascular malformations can be caused by mutations in various genes controlling cellular growth and division. It has also become clear that these mutations occur during development and are often present in only a small percentage of cells, explaining why patients develop local overgrowth of the vasculature and the rest of the body is relatively unaffected.
To understand how these vascular malformations grow and develop it is important to understand how the initially few mutant cells divide and develop into large vascular lesions.  Another possibility is that mutant cells stimulate the healthy cells of patients not carrying the mutation to also start to grow and divide.

Cells constantly divide and give rise to identical daughter-cells which in turn again divide in a process called clonal expansion. To understand if vascular malformations arise from such clonal expansion of mutant cells, we label individual cells with a distinct color by expressing different colorful proteins in the cell’s nucleus. As the cell divides the daughter cells will carry the same colored protein and we can observe which cells are related to one another.

Using this approach, we investigate how cells in vascular lesions are organized and if they originate from one mutant cell which expanded in a clonal fashion or if healthy cells also contribute to the malformation.

 
About the author:

Hans is a PhD student in the group of Taija Mäkinen at the Rudbeck laboratory. As part of the European Marie Curie ITN project ‘V.A. cure’ he tries to understand the mechanisms and processes involved in the formation of venous and lymphatic malformations.

Photo of Hans SchoofsHans Schoofs
Uppsala University
Dept. Immunology, Genetics and Pathology
Rudbeck Laboratory C11
Dag Hammarskjölds Väg 20
751 85 Uppsala
Sweden

vacure.eu
www.makinenlab.com
www.igp.uu.se/research/vascular-biology/taija-makinen/
twitter.com/hansschoofs

Mouse model for clonal labelling, generated by the lab of Rui Benedito (CNIC, Madrid): (Pontes-Quero et al., 2017) https://www.cell.com/cell/comments/S0092-8674(17)30867-X