Authors
Qilin Gu, Xiaojie Yang, Jie Lv, Jiaxiong Zhang, BO Xia, Jun-dae Kim, Ruoyu Wang, Feng Xiong, Shu Meng, Thomas P Clements, Bhavna Tandon, Daniel S Wagner, Miguel F Diaz, Pamela L Wenzel, Yury I Miller, David Traver, John P Cooke, Wenbo Li, Leonard I Zon, Kaifu Chen, Yongping Bai, Longhou Fang
Publication date
2019/3/8
Journal
Science
Volume
363
Issue
6431
Pages
1085-1088
Publisher
American Association for the Advancement of Science
Description
Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by …
Scholar articles
Q Gu, X Yang, J Lv, J Zhang, BO Xia, J Kim, R Wang… - Science, 2019