Transcription factor Prox1 as a regulator of skeletal muscle stem cell differentiation and rhabdomyosarcoma.
Cardiovascular diseases rank among the most life-threatening diseases and are a continuously increasing global problem in aging populations. Despite some progress in treatment options, the clinical prognosis of heart failure is currently worse than that of most cancers.
Endothelial cells in different organs have been shown to express a unique combination of transcription factors, angiogenic growth factors, adhesion molecules and chemokines. This reflects the varying needs of different organs for e.g. oxygen and nutrient supply. In response to different stimuli, ECs secrete a set of proteins, which can act on the various neighbouring cell types. It is estimated that humans have about 100000 km of blood vessels, which most likely makes the vasculature the largest endocrine organ in the body.
Our research is focused on studying how endothelial cell transcriptome and secretome is changed by common cardiometabolic risk factors such as aging, physical inactivity and obesity. We also aim to decipher the molecular mechanisms mediating the health benefits of exercise to identify novel targets in endothelial cells for cardiovascular diseases.
Unlike the heart, skeletal muscles have a remarkable capacity for regeneration. We have shown that Prox1 transcription factor, which regulates stem cell behaviour in various healthy and malignant tissues, is essential for slow muscle fiber type and satellite cell differentiation in skeletal muscle (Kivelä et al. Nature Communications 2016). Interestingly, several genome-wide association studies have also identified Prox1 as one of the strongest candidate genes in type 2 diabetes in various populations.
We have also uncovered an essential role of Prox1 in rhabdomyosarcoma, which is a pediatric soft tissue cancer resembling skeletal muscle. We have shown that Prox1 is needed for rhabdomyosarcoma growth and stemness and uncovered potential treatment targets downstream of Prox1 (PNAS 2022, EMBO Mol Med 2025).