Invariant asymmetry renews the lymphatic vasculature during homeostasis

Journal of Translational Medicine

Research

Richard M. Tempero¹  Alicia L. Connor¹  Philip M. Kelley¹ 

[1] Department of Neurosensory Genetics and Otolaryngology and Head and Neck Surgery, Boys Town National Research Hospital, 555 North 30th Street, 68131, Omaha, NE, USA;

关键词: Lymphatic Vessel;    Live Imaging;    Lymphatic Endothelial Cell;    Intravital Microscopy;    Lymphatic Vasculature;   

DOI  :  10.1186/s12967-016-0964-z

 received in 2016-01-25, accepted in 2016-06-28,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe lymphatic vasculature regulates tissue physiology and immunity throughout life. The self renewal mechanism that maintains the lymphatic vasculature during conditions of homeostasis is unknown. The purpose of this study was to investigate the cellular mechanism of lymphatic endothelial cell (LEC) self renewal and lymphatic vessel maintenance.MethodsInductive genetic techniques were used to label LECs with tandem dimer tomato (tdT) in adult mice. Two types of studies were performed, those with high dose inductive conditions to label nearly all the lymphatic vessels and studies with low dose inductive conditions to stochastically label individual clones or small populations of LECs. We coupled image guidance techniques and live fluorescence microscopy imaging with lineage tracing to track the fate of entire tdT+ cutaneous lymphatic vessels or the behavior of individual or small populations of LECs over 11 months. We tracked the fate of 110 LEC clones and 80 small LEC populations (clusters of 2–7 cells) over 11 months and analyzed their behavior using quantitative techniques.ResultsThe results of the high dose inductive studies showed that the lymphatic vessels remained tdT+ over 11 months, suggesting passage and expression of the tdT transgene from LEC precursors to progenies, an intrinsic model of self- renewal. Interestingly, the morphology of tdT+ lymphatic vasculature appeared relatively stable without significant remodeling during this time period. By following the behavior of labeled LEC clones or small populations of LECs individually over 11 months, we identified diverse LEC fates of proliferation, quiescence, and extinction. Quantitative analysis of this data revealed that the average lymphatic endothelial clone or small population remained stable in size despite diverse individual fates.ConclusionThe results of these studies support a mechanism of invariant asymmetry to self renew the lymphatic vasculature during homeostasis. These original findings raise important questions related to the plasticity and self renewal properties that maintain the lymphatic vasculature during life.

【 授权许可】

CC BY   
© The Author(s) 2016