Control of perivascular cell differentiation by endothelial cells


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PhD thesis: a PhD thesis.
Control of perivascular cell differentiation by endothelial cells
Wetterwald Laureline
Petrova Tatiana
Sabine Amelie
Institution details
Université de Lausanne, Faculté de biologie et médecine
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Blood vasculature is indispensable for embryonic development, tissue regeneration and normal organ homeostasis. The development of a functional vascular network is a complex process requiring a coordinated response of endothelial and perivascular cells, adjusted to the organ needs. Its dysfunction is tightly linked to multiple human pathologies, such as cardiovascular diseases, hypertension, diabetes, obesity, chronic inflammatory diseases and cancer. To date, several important molecular players have been identified that regulate multiple aspects of vascular development, such as sprouting angiogenesis, or maintenance of mature vascular structures. However, while targeted anti-angiogenic therapies are efficient in some diseases such as neovascular age-related macular degeneration, their application has met only limited success for treatment of cancer. These limitations highlight the need for further identification of novel molecular regulators vascular function and their extensive characterization in organ- and disease-specific contexts. Here we report the characterization of Myc target 1 (Myct1), a novel evolutionary conserved endothelial transmembrane protein that regulates the fate of perivascular cells. To study Myct1 function in the vasculature, we generated mice with endothelial-specific ablation of Myct1. We found that Myct1 controls pericyte recruitment both during physiological and pathological angiogenesis. Moreover, we observed that Myct1 promotes adipose tissue expansion by regulating de novo adipogenesis. At the molecular level, we found that Myct1 is a transmembrane phosphoprotein regulating the interplay between the TGFβ and mTOR signaling pathways. Our results generate new fundamental knowledge about the crosstalk of endothelial and perivascular cells during homeostasis and pathological situations. Impaired vascular maturation is an important feature of many pathological conditions, such as cancer, therefore targeting Myct1 may open additional possibilities for treating several common human diseases.
Blood vessels - Endothelial cells - Angiogenesis - Adipose tissue development
Create date
27/08/2020 17:05
Last modification date
18/11/2020 7:26
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