Regulation of plasticity in cardiovascular health and disease
Tissue homeostasis and regeneration after injury rely on mobilisation of tissue resident stem and progenitor cells or de-differentiation of functional cell types. Our group investigates the regulation of such cell plasticity in the cardiovascular system and how this is perturbed in disease. Our recent work demonstrates that a small number of cells proliferate extensively to form lesions in vascular disease models.
Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels. Dobnikar L/Taylor AL, Chappell J, Oldach P, Harman JL, Oerton E, Dzierzak E, Bennett MR, Spivakov M, Jorgensen HF. (2018). Nature Communications 9, 4567.
Extensive Proliferation of a Subset of Differentiated, Yet Plastic, Medial Vascular Smooth Muscle Cells Contribute to Neointimal Formation in Mouse Injury and Atherosclerosis Models. Chappell J, Harman JL, Narasimhan VM, Yu H, Foote K, Simons BD, Bennett MR and Jorgensen HF. Circ Res. September 2016.
Transcriptional Mechanisms of Proneural Factors and REST in Regulating Neuronal Reprogramming of Astrocytes. Masserdotti G., Gillotin S., Sutor B., Drechsel D., Irmler M., Jørgensen H.F., Sass S., Theis F.J., Beckers J., Berninger B., Guillemot F., Götz M. (2015). Cell Stem Cell, 17:74-88.
Embryonic stem cell-derived hemangioblasts remain epigenetically plastic and require PRC1 to prevent neural gene expression. *Mazzarella, L.*, Jørgensen, H.F.*, Terry, A., Kouskoff V., Merkenschlager M., Fisher, A.G. (2011). Blood, 117: 83-87. (*: equal contribution).
Is REST required for ESC pluripotency? Jørgensen, H.F., Chen, Z.-F., Merkenschlager, M., Fisher, A.G. (2009). Nature, 457, E4-5.
REST selectively represses a subset of RE1-containing neuronal genes in mouse embryonic stem cells. Development, 136, 715-21. Jørgensen, H.F., Terry, A., Beretta, C., Peirera, C.F., LeLeu, M., Chen, Z.-F., Merkenschlager, M., Fisher, A.G. (2009).