Genome-wide functional analysis reveals central signaling regulators of lymphatic endothelial cell migration and remodeling
Steven P Williams, Adam F Odell, Tara Karnezis, Rae H Farnsworth, Cathryn M Gould, Jason Li, Sophie Paquet-Fifield, Nicole C Harris, Anne Walter, Julia L Gregory, Sara F Lamont, Ruofei Liu, Elena A Takano, Cameron J Nowell, Neil I Bower, Daniel Resnick, Gordon K Smyth, Leigh Coultas, Benjamin M Hogan, Stephen B Fox Show all
SCIENCE SIGNALING | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2017
Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration. We compared our data set with mRNA differential expression data from endothelial and stromal cells derived from two in vivo models of lymphat..View full abstract
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We thank M. Macheda and S. Roufail for technical assistance, D. Thomas and Y. Handoko for screening assistance, K. Amarasinghe for bioinformatics assistance, and P. Kaur (Peter MacCallum Cancer Centre) for providing primary human dermal fibroblasts. We also thank J. Taylor for assistance in generating the figures. Funding: This work was funded partly by a program grant from the National Health and Medical Research Council of Australia (NHMRC). S.A.S. and M.G.A. were supported by Senior Research Fellowships from the NHMRC. S.A.S. acknowledges the support of the Pfizer Australia Fellowship. S.P.W. received a Doctoral Research Scholarship from the National Breast Cancer Foundation. N.C.H. and R.L. received a Melbourne Research Scholarship from the University of Melbourne. G.K.S. was supported by an NHMRC Program Grant and Fellowship. S.N.M. and L.C. were supported by Future Fellowships from the Australian Research Council. The Victorian Centre for Functional Genomics was funded by the Australian Cancer Research Foundation, the Victorian Department of Industry, Innovation, and Regional Development, the Australian Phenomics Network supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative, the Australasian Genomics Technologies Association, the Jack Brockhoff Foundation, and the Peter MacCallum Foundation.