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    Genetic lineage tracing identifies endocardial origin of liver vasculature

    2016/5/31 Viewers:
    Genetic lineage tracing identifies endocardial origin of liver vasculature

    Hui Zhang, Wenjuan Pu, Xueying Tian, Xiuzhen Huang, Lingjuan He, Qiaozhen Liu, Yan Li, Libo Zhang, Liang He, Kuo Liu, Astrid Gillich & Bin Zhou

    Nature Genetics 48, 537–543 (2016) doi:10.1038/ng.3536
    Received 06 January 2016 Accepted 04 March 2016 Published online 28 March 2016

    Abstract

    The hepatic vasculature is essential for liver development, homeostasis and regeneration, yet the developmental program of hepatic vessel formation and the embryonic origin of the liver vasculature remain unknown. Here we show in mouse that endocardial cells form a primitive vascular plexus surrounding the liver bud and subsequently contribute to a substantial portion of the liver vasculature. Using intersectional genetics, we demonstrate that the endocardium of the sinus venosus is a source for the hepatic plexus. Inhibition of endocardial angiogenesis results in reduced endocardial contribution to the liver vasculature and defects in liver organogenesis. We conclude that a substantial portion of liver vessels derives from the endocardium and shares a common developmental origin with coronary arteries.

    Figure 4 Sinus venosus endocardium contributes to liver vasculature. (a) Wholemount views of E10.5 embryos from lineage tracing strategy 1 (Nfatc1-dre; Rosa26-RSRRFP) and strategy 2 (Nfatc1-dre; Npr3-creER; Ai66). SV is labeled by Nfatc1-drein strategy 1 but not by Nfatc1-drein strategy 2. Tamoxifen was injected at E8 for both strategies. H, heart. Magnified views of the boxed regions are shown to the right. (b) Immunostaining for RFP, HNF4A and PECAM1 on E10.5 embryonic sections. Liver vasculature and SV are labeled by Nfatc1-drein strategy 1 but not by Nfatc1-drein strategy 2. Insets are bright-field images. (c) Whole-mount views of E13.5 hearts and livers from strategies 1 and 2. (d) Immunostaining for RFP and PECAM1 on heart and liver sections from strategies 1 and 2. (e) Schematic showing the proximity of the developing caudal endocardium to the liver bud and the contribution of SV endocardium to the primitive liver vasculature at E8.0–E9.5. With SV withdrawal to the chest and diaphragm formation, SV endocardium contributes to coronary vessels. Scale bars: 1 mm in a, 100 µm in band d, 0.5 mm in c.

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