Journal article
Liver X Receptors and Oxysterols Promote Ventral Midbrain Neurogenesis In Vivo and in Human Embryonic Stem Cells
P Sacchetti, KM Sousa, AC Hall, I Liste, KR Steffensen, S Theofilopoulos, CL Parish, C Hazenberg, LA Richter, O Hovatta, JA Gustafsson, E Arenas
Cell Stem Cell | Published : 2009
Abstract
Control over progenitor proliferation and neurogenesis remains a key challenge for stem cell neurobiology and a prerequisite for successful stem cell replacement therapies for neurodegenerative diseases like Parkinson's disease (PD). Here, we examined the function of two nuclear receptors, liver X receptors (Lxrα and β) and their ligands, oxysterols, as regulators of cell division, ventral midbrain (VM) neurogenesis, and dopaminergic (DA) neuron development. Deletion of Lxrs reduced cell cycle progression and VM neurogenesis, resulting in decreased DA neurons at birth. Activation of Lxrs with oxysterol ligands increased the number of DA neurons in mouse embryonic stem cells (ESCs) and in wil..
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Awarded by Michael J. Fox Foundation for Parkinson's Research
Funding Acknowledgements
The authors are grateful to Drs. Magdalena Gbtz, Weimin Zhong, and Franqois Guillemot for their invaluable comments and critical support of this work. We also thank Heider Andre for comments and suggestions on the manuscript, Dr. Ruani Fernando for invaluable discussion and technical help on histology and imaging, and Johnny Soderlund for technical assistance. This work was supported by the Michael J. Fox Foundation, Swedish Foundation for Strategic Research (INGVAR and CEDB), European Union (Strokemap, NeuroStemCell), Karolinska Institutet, Petrus and Augusta Hedlunds Foundation, Swedish Research Council (VR2008:3287 and DBRM), and Norwegian Research Council to E.A., and grants from VIR to O.H., L.A.R., and J.-A.G. E.A. was supported by Swedish Royal Academy of Sciences and Knut and Alice Wallenberg Foundation, P.S. was supported by Norwegian Research Council, and A.C.H. was supported by Human Frontiers Science Program. C.L.P. was supported by an Australian National Health and Medical Research Council (NHMRC) CJ Martin Fellowship and NHMRC Career Development Award. J.-A.G. is shareholder and consultant of KaroBio AB and was supported by a grant from KaroBio AB.