Background: The 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.
Methods: Inductive 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.
Results: The 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.
Conclusion: The 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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940917 | PMC |
| http://dx.doi.org/10.1186/s12967-016-0964-z | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Immature Smooth Muscle Infiltration in Sporadic Lymphangioleiomyomatosis: A Case Study.
S D Med
November 2024
Sanford USD Medical Center, Sioux Falls, South Dakota.
Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that causes progressive pulmonary damage. It typically affects young reproductive-age females with tuberous sclerosis complex (TSC). The clinical manifestations of LAM result from the progressive invasion of abnormal smooth muscle cells into lung parenchyma, lymphatics, or pulmonary vasculature.
View Article and Find Full Text PDFSodium-Directed Crosstalk Between Immune Cells and Lymphatic Vessels.
Curr Hypertens Rep
January 2025
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
Purpose Of Review: The role of the lymphatic system in clearing extravasated fluids, lipid transport, and immune surveillance is well established, and lymphatic vasculature can provide a vital role in facilitating crosstalk among various organ systems. Lymphatic vessels rely on intrinsic and local factors to absorb and propel lymph from the interstitium back to the systemic circulation. The biological implications of local influences on lymphatic vessels are underscored by the exquisite sensitivity of these vessels to environmental stimuli.
View Article and Find Full Text PDFThe central nervous system (CNS) parenchyma has conventionally been believed to lack lymphatic vasculature, likely due to a non-permissive microenvironment that hinders the formation and growth of lymphatic endothelial cells (LECs). Recent findings of ectopic expression of LEC markers including Prospero Homeobox 1 (PROX1), a master regulator of lymphatic differentiation, and the vascular permeability marker Plasmalemma Vesicle Associated Protein (PLVAP), in certain glioblastoma and brain arteriovenous malformations (AVMs), has prompted investigation into their roles in cerebrovascular malformations, tumor environments, and blood-brain barrier (BBB) abnormalities. To explore the relationship between ectopic LEC properties and BBB disruption, we utilized endothelial cell-specific overexpression mutants.
View Article and Find Full Text PDFLymphatic collection and cell isolation from mouse models for multiomic profiling.
Nat Protoc
January 2025
Department of Molecular Metabolism, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Premetastatic cancer cells often spread from the primary lesion through the lymphatic vasculature and, clinically, the presence or absence of lymph node metastases impacts treatment decisions. However, little is known about cancer progression via the lymphatic system or of the effect that the lymphatic environment has on cancer progression. This is due, in part, to the technical challenge of studying lymphatic vessels and collecting lymph fluid.
View Article and Find Full Text PDFApplication of Laparoscopic Partial Splenectomy with Total Blood Flow Occlusion in Benign Splenic Lesions.
J Vis Exp
December 2024
Department of Hepatobiliary and Pancreatic-Spleen Surgery, Shunde Hospital of Southern Medical University, First People's Hospital of Shunde;
Laparoscopic partial splenectomy (LPS) is gradually becoming the preferred method for treating benign splenic lesions. However, due to the abundant blood supply and its soft, fragile tissue texture, especially when the lesion is located near the splenic hilum or is particularly large, performing partial splenectomy (PS) in clinical practice is extremely challenging. Therefore, we have been continuously exploring and optimizing hemorrhage control methods during PS, and we here propose a method to perform LPS with complete spleen blood flow occlusion.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!