Vorschau

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Abstract

Imprinted genes in placental mammals play a critical role in regulating prenatal growth and setting the metabolic rate of development. Highly expressed in embryos and early postnatal life, imprinted genes are down regulated when the organism reaches adulthood, remaining expressed in individual cells where they control activation and plasticity. Maternally imprinted gene Pw1, also known as Peg3, recently was described as a potential adult stem cell marker in various tissues such as bone marrow, central nervous system and intestines. In skeletal muscle it marks myogenic stem cells, which are located in interstitia and can efficiently contribute to muscle regeneration after focal freeze-crush injury. Using a transgenic Pw1:nLacZ reporter mouse, I described a subpopulation of proepicardial/epicardial derived mesenchymal cells involved in maintaining homeostasis of adult mouse heart through secretion of various growth factors. Immunohistochemistry and cytometric analysis revealed that myocardial Pw1 cells express the cardiac stem cell membrane receptors Sca1, Pdgfra, Cd34 and Cd29, making them a potentially interesting component of regenerative medicine for further investigation. Based on mRNA expression profiles and patterns during embryonic development I surmise an epicardial origin of Pw1 cells and their involvement in cardiac growth, as adult Pw1 cells are highly pro-angiogenic in vitro and can induce tube formation when they are co-cultured with an endothelial cell line. To investigate the role of Pw1 cells during postnatal cardiac growth I have linked their action to heart hypertrophy during pregnancy. Using pharmacological tools I locally depleted Pw1 cells which resulted in local cardiomyocyte atrophy and fibrosis. To explore the remodelling potential of Pw1 cells in pathological conditions we are planning to investigate their involvement in disease models of myocardial infarction.