A chemical small molecule induces mouse embryonic stem cell differentiation into functional vascular endothelial cells via Hmbox1.
Embryonic stem cells (ESCs) can differentiate to endothelial progenitor cells and vascular endothelial cells (VECs), but the mechanism is largely unknown. In this study, we synthesized 2 chiral compounds (R-ABO and S-ABO) and identified R-ABO as an effective inducer of ESC differentiation into VECs. Furthermore, we found that R-ABO induced ESC differentiation into VECs via homeobox containing 1 (Hmbox1) that acted upstream of fibroblast growth factor 2 (FGF-2). The data suggest that R-ABO is a novel tool for ESC differentiation into VECs, and Hmbox1 is a key regulator in this differentiation process. These findings provide information on a novel target and a new platform for further investigating the gene control of ESC differentiation to VECs.
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Jinan, China.
Lei
L
Han
Jing
J
Shao
Le
L
Su
Jiangang
J
Gao
Shengqing
S
Wang
Yun
Y
Zhang
Shangli
S
Zhang
Baoxiang
B
Zhao
Junying
J
Miao
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D000077214:Becaplermin; D048588:Benzoxazines / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D039663:Integrin beta4 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D018919:Neovascularization, Physiologic; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D013237:Stereoisomerism; D015533:Transcriptional Activation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C541593:6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine; D043925:Angiogenesis Inducing Agents; D048588:Benzoxazines; C578573:Hmbox1 protein, mouse; D018398:Homeodomain Proteins; D039663:Integrin beta4; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin