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DOI | 10.1038/nature14569 |
Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment | |
Li, Pulin1,2,3,4; Lahvic, Jamie L.1,2,3; Binder, Vera1,2,3,5; Pugach, Emily K.1,2,3; Riley, Elizabeth B.1,2,3; Tamplin, Owen J.1,2,3; Panigrahy, Dipak6; Bowman, Teresa V.1,2,3; Barrett, Francesca G.1,2,3; Heffner, Garrett C.1,2,3; McKinney-Freeman, Shannon7; Schlaeger, Thorsten M.1,2,3; Daley, George Q.1,2,3; Zeldin, Darryl C.8; Zon, Leonard I.1,2,3,4 | |
发表日期 | 2015-07-23 |
ISSN | 0028-0836 |
卷号 | 523期号:7561页码:468-U203 |
英文摘要 | Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions such as leukaemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here we develop a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We use this system to conduct a chemical screen, and identify epoxyeicosatrienoic acids (EETs) as a family of lipids(1,2) that enhance HSPC engraftment. The pro-haematopoietic effects of EETs were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique activator protein 1 (AP-1) and runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the phosphatidylinositol-3-OH kinase (PI(3) K) pathway, specifically PI(3) K gamma. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate several cellular processes, such as migration, to promote engraftment. Furthermore, we demonstrate that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study establishes a new method to explore the molecular mechanisms of HSPC engraftment, and discovers a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation. |
语种 | 英语 |
WOS记录号 | WOS:000358378900038 |
来源期刊 | NATURE |
来源机构 | 美国环保署 |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/61418 |
作者单位 | 1.Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA; 2.Harvard Univ, Sch Med, Boston Childrens Hosp, Div Haematol Oncol, Boston, MA 02115 USA; 3.Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA; 4.Harvard Univ, Chem Biol Program, Cambridge, MA 02138 USA; 5.Univ Munich, Dr von Hauner Childrens Hosp, Dept Hematol & Oncol, D-80337 Munich, Germany; 6.Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA 02115 USA; 7.St Jude Childrens Res Hosp, Dept Haematol, Memphis, TN 38105 USA; 8.Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA |
推荐引用方式 GB/T 7714 | Li, Pulin,Lahvic, Jamie L.,Binder, Vera,et al. Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment[J]. 美国环保署,2015,523(7561):468-U203. |
APA | Li, Pulin.,Lahvic, Jamie L..,Binder, Vera.,Pugach, Emily K..,Riley, Elizabeth B..,...&Zon, Leonard I..(2015).Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment.NATURE,523(7561),468-U203. |
MLA | Li, Pulin,et al."Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment".NATURE 523.7561(2015):468-U203. |
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