Development of stabilin2+ endothelial cells from mouse embryonic stem cells by inhibition of TGFbeta/activin signaling.
To understand the endothelial cell (EC) development, arterial, venous, and lymphatic EC (LEC) have been successfully induced from embryonic stem cells (ESC). However, tissue-specific EC, such as hepatic sinusoidal EC (HSEC), have never been generated from ESC. Based on the findings that TGFbeta/activin signaling negatively regulates differentiation of both LEC and HSEC, and that HSEC and LEC are distinguishable by the expression of marker genes, we assessed the role of TGFbeta/activin signaling in EC development from ESC. Here we show that the inhibition of TGFbeta/activin signaling by a TGFbeta receptor I (TGFbetaRI) kinase inhibitor increased the expression of Lyve1 and stabilin2 but not podoplanin in CD31+CD34+ EC derived from ESC. EC generated by the inhibition of TGFbetaRI signaling also exhibited stronger endocytic activity than control EC, indicating that their phenotype is similar to fetal HSEC. Our results reveal that TGFbeta/activin signaling negatively regulates the early events of HSEC differentiation.
Nonaka
Hidenori
H
Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan; Japan Health Sciences Foundation, Chuo-ku, Tokyo, Japan.
Watabe
Tetsuro
T
Saito
Shigeru
S
Miyazono
Kohei
K
Miyajima
Atsushi
A
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors; D028341:Activins / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis / Q000235:genetics; D002454:Cell Differentiation; D002462:Cell Membrane; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics; D008099:Liver / Q000098:blood supply; D026901:Membrane Transport Proteins; D051379:Mice; D010641:Phenotype; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000502:physiology
D030201:Activin Receptors, Type I; D028341:Activins; D015816:Cell Adhesion Molecules, Neuronal; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D016212:Transforming Growth Factor beta; C486733:Stab2 protein, mouse; C492273:LYVE1 protein, mouse