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DOI | 10.1126/science.aav1749 |
AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate | |
Gu, Qilin1; Yang, Xiaojie1; Lv, Jie1,2; Zhang, Jiaxiong1,3; Xia, Bo1,2; Kim, Jun-dae1; Wang, Ruoyu4,5,6; Xiong, Feng4,5; Meng, Shu1; Clements, Thomas P.7; Tandon, Bhavna7; Wagner, Daniel S.7; Diaz, Miguel F.8; Wenzel, Pamela L.8; Miller, Yury I.9; Traver, David10; Cooke, John P.1,11,12; Li, Wenbo4,5,6; Zon, Leonard I.13,14,15; Chen, Kaifu1,2,11,12; Bai, Yongping3; Fang, Longhou1,11,12,16 | |
2019-03-08 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 363期号:6431页码:1085-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Peoples R China |
英文摘要 | 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 upregulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000460750100049 |
WOS关键词 | AORTIC ENDOTHELIUM ; ZEBRAFISH ; PATHWAY ; SREBP ; ANGIOGENESIS ; ACCUMULATION ; SYSTEM ; NOTCH1 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/200918 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Houston Methodist, Ctr Cardiovasc Regenerat, 6550 Fannin St, Houston, TX 77030 USA; 2.Houston Methodist, Dept Cardiovasc Sci, Ctr Bioinformat & Computat Biol, 6550 Fannin St, Houston, TX 77030 USA; 3.Cent S Univ, Xiangya Hosp, Dept Geriatr Med, Changsha, Hunan, Peoples R China; 4.Univ Texas MD Anderson Canc Ctr, UTHlth McGovern Med Sch, Dept Biochem & Mol Biol, Houston, TX 77030 USA; 5.UTHlth Houston, Houston, TX 77030 USA; 6.Univ Texas MD Anderson Canc Ctr, Grad Sch Biomed Sci, Houston, TX 77030 USA; 7.Rice Univ, Dept Biosci, Houston, TX 77005 USA; 8.Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Childrens Regenerat Med Program, Dept Pediat Surg,Ctr Stem Cell & Regenerat Med, Houston, TX 77030 USA; 9.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA; 10.Univ Calif San Diego, Div Biol Sci, Dept Cellular & Mol Med, La Jolla, CA 92093 USA; 11.Houston Methodist, Houston Methodist Res Inst, Houston Methodist Inst Acad Med, 6550 Fannin St, Houston, TX 77030 USA; 12.Cornell Univ, Weill Cornell Med Coll, Dept Cardiothorac Surg, Ithaca, NY 10065 USA; 13.Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA; 14.Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA; 15.Harvard Med Sch, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA; 16.Houston Methodist, Dept Obstet & Gynecol, 6550 Fannin St, Houston, TX 77030 USA |
推荐引用方式 GB/T 7714 | Gu, Qilin,Yang, Xiaojie,Lv, Jie,et al. AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate[J]. SCIENCE,2019,363(6431):1085-+. |
APA | Gu, Qilin.,Yang, Xiaojie.,Lv, Jie.,Zhang, Jiaxiong.,Xia, Bo.,...&Fang, Longhou.(2019).AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate.SCIENCE,363(6431),1085-+. |
MLA | Gu, Qilin,et al."AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate".SCIENCE 363.6431(2019):1085-+. |
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