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Invariant asymmetry renews the lymphatic vasculature during homeostasis.

Connor AL, Kelley PM, Tempero RM - J Transl Med (2016)

Bottom Line: Interestingly, the morphology of tdT(+) lymphatic vasculature appeared relatively stable without significant remodeling during this time period.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosensory Genetics and Otolaryngology and Head and Neck Surgery, Boys Town National Research Hospital, 555 North 30th Street, Omaha, NE, 68131, USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Cartoon showing a multicolor model of lymphatic endothelial clonal subunits. For schematic purposes, a mosaic of lymphatic clonal subunits is shown comprised of individual LECs, each represented by a different color. Lymphatic endothelial clonal evolution conforming to a model of invariant asymmetry will predictably result in a mosaic of lymphatic endothelial subunits
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Fig7: Cartoon showing a multicolor model of lymphatic endothelial clonal subunits. For schematic purposes, a mosaic of lymphatic clonal subunits is shown comprised of individual LECs, each represented by a different color. Lymphatic endothelial clonal evolution conforming to a model of invariant asymmetry will predictably result in a mosaic of lymphatic endothelial subunits

Mentions: The results of this study show that LEC self renewal and lymphatic endothelial clonal units are major mechanisms of lymphatic vessel homeostasis. The data suggests that the peripheral lymphatic vasculature is a slow cycling organ system during homeostasis. The results are consistent with an invariant asymmetry model of self renewal resulting in a mosaic of ‘lymphatic endothelial units’ (Fig. 7). Understanding how these lymphatic clonal units regulate lymphatic vessel growth and remodeling during homeostasis and disease conditions may provide useful therapeutic concepts and targets to contract or expand the lymphatic vasculature.Fig. 7


Invariant asymmetry renews the lymphatic vasculature during homeostasis.

Connor AL, Kelley PM, Tempero RM - J Transl Med (2016)

Cartoon showing a multicolor model of lymphatic endothelial clonal subunits. For schematic purposes, a mosaic of lymphatic clonal subunits is shown comprised of individual LECs, each represented by a different color. Lymphatic endothelial clonal evolution conforming to a model of invariant asymmetry will predictably result in a mosaic of lymphatic endothelial subunits
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4940917&req=5

Fig7: Cartoon showing a multicolor model of lymphatic endothelial clonal subunits. For schematic purposes, a mosaic of lymphatic clonal subunits is shown comprised of individual LECs, each represented by a different color. Lymphatic endothelial clonal evolution conforming to a model of invariant asymmetry will predictably result in a mosaic of lymphatic endothelial subunits
Mentions: The results of this study show that LEC self renewal and lymphatic endothelial clonal units are major mechanisms of lymphatic vessel homeostasis. The data suggests that the peripheral lymphatic vasculature is a slow cycling organ system during homeostasis. The results are consistent with an invariant asymmetry model of self renewal resulting in a mosaic of ‘lymphatic endothelial units’ (Fig. 7). Understanding how these lymphatic clonal units regulate lymphatic vessel growth and remodeling during homeostasis and disease conditions may provide useful therapeutic concepts and targets to contract or expand the lymphatic vasculature.Fig. 7

Bottom Line: Interestingly, the morphology of tdT(+) lymphatic vasculature appeared relatively stable without significant remodeling during this time period.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosensory Genetics and Otolaryngology and Head and Neck Surgery, Boys Town National Research Hospital, 555 North 30th Street, Omaha, NE, 68131, USA.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus