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Review
. 2020 Jul 6;21(13):4790.
doi: 10.3390/ijms21134790.

Cell Fate Determination of Lymphatic Endothelial Cells

Young Jae Lee  1   2
Affiliations
Review

Cell Fate Determination of Lymphatic Endothelial Cells

Young Jae Lee. Int J Mol Sci. .

Abstract

The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake, and immune responses. Defects in the lymphatic system are associated with various diseases such as lymphedema, atherosclerosis, fibrosis, obesity, and inflammation. The first step in lymphangiogenesis is determining the cell fate of lymphatic endothelial cells. Several genes involved in this commitment step have been identified using animal models, including genetically modified mice. This review provides an overview of these genes in the mammalian system and related human diseases.

Keywords: cell fate; genetically modified mice; lymphangiogenesis; lymphatic endothelial cells; lymphatic vessels.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Genes and signaling pathways involved in the cell fate determination of lymphatic endothelial cells. PROX1 is the master regulator to determine the fate of lymphatic endothelial cells. Several genes act as transcriptional activators (NR2F2, SOX18, and HHEX) or repressors (YAP1 and TAZ). RAF1/ERK signaling activates SOX18 and PROX1 expression. MiRNAs, Mir181a and Mir31, are post-transcriptional regulators of PROX1. The sumoylation of PROX1 by SUMO1 modulates the DNA binding and transcriptional activities of PROX1. BMP2 signaling negatively regulates PROX1 expression through an increase of Mir181a and Mir31 expression. NOTCH and NR2F2 mutually inhibit their expression, and NOTCH downregulates PROX1 and NR2F2 expression via HEY1 and HEY2. BMP9/ACVRL1 signaling inhibits PROX1 expression. TMEM100, a downstream target of BMP9/ACVRL1 signaling, activates NOTCH signaling. VEGFC is a lymphangiogenic growth factor and the ligand of FLT4. VEGFC-FLT4 signaling that is a main downstream effector of PROX1 is essential for the budding-off of lymphatic endothelial cells from the cardinal vein. Downregulation of Mir126 attenuates FLT4 signaling. Interaction between FLT4 and ITGB1, which is interfered with by ILK (integrin-linked kinase) is important for the activation of FLT4 signaling.
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References

    1. Kesler C.T., Liao S., Munn L.L., Padera T.P. Lymphatic vessels in health and disease. Wiley Interdiscip. Rev. Syst. Biol. Med. 2013;5:111–124. doi: 10.1002/wsbm.1201. - DOI - PMC - PubMed
    1. Alitalo K., Tammela T., Petrova T.V. Lymphangiogenesis in development and human disease. Nature. 2005;438:946–953. doi: 10.1038/nature04480. - DOI - PubMed
    1. Coso S., Bovay E., Petrova T.V. Pressing the right buttons: Signaling in lymphangiogenesis. Blood. 2014;123:2614–2624. doi: 10.1182/blood-2013-12-297317. - DOI - PubMed
    1. Escobedo N., Oliver G. Lymphangiogenesis: Origin, Specification, and Cell Fate Determination. Annu. Rev. Cell Dev. Biol. 2016;32:677–691. doi: 10.1146/annurev-cellbio-111315-124944. - DOI - PubMed
    1. Kim K.R., Lee E.Y., Shaikh R. Pediatric Body MRI. Springer; Berlin/Heidelberg, Germany: 2020. Lymphatics; pp. 113–124.