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| Status |
Public on Jul 13, 2015 |
| Title |
Epoxyeicosatrienoic Acids Enhance Haematopoietic Stem and Progenitor Cell Specification and Engraftment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Haematopoietic stem and progenitor cell (HSPC) transplant is a widely used treatment for life-threatening conditions including leukemia; however, the molecular mechanisms regulating HSPC engraftment of the recipient niche remain incompletely understood. Here, we developed a competitive HSPC transplant method in adult zebrafish, using in vivo imaging as a non-invasive readout. We used this system to conduct a chemical screen and identified epoxyeicosatrienoic acids (EET) as a family of lipids that enhance HSPC engraftment. EETs’ pro-haematopoietic effects are conserved in the developing zebrafish, where this molecule promotes HSPC specification through activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect requires the activation of PI3K pathway, specifically PI3Kg. In adult HSPCs, EETs induce transcriptional programs including AP-1 activation, modulating multiple cellular processes, such as migration, to promote engraftment. Finally, we demonstrated that the EET effects on enhancing HSPC homing and engraftment are conserved in mammals. Our study established a novel method to explore the molecular mechanisms of HSPC engraftment, and discovered a previously unrecognized, evolutionarily conserved pathway regulating multiple haematopoietic generation and regeneration processes. EETs may have clinical application in marrow or cord blood transplantation.
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| Overall design |
To analyze the effect of 11,12-EET on gene expression of human blood cells, we treated human CD34+ cells (positively selected from cord blood) and the human leukemic cell line U937 with 5uM 11,12-EET for 2 hrs. Control treatment was done with DMSO.
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| Contributor(s) |
Binder V, Yang S |
| Citation(s) |
26201599 |
| Submission date |
Mar 10, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Leonard Zon |
| E-mail(s) |
zon@enders.tch.harvard.edu
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| Organization name |
Boston Children's Hospital
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| Department |
Oncology/Hematology
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| Street address |
1 Blackfan Circle
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (2) |
| GPL9052 |
Illumina Genome Analyzer (Homo sapiens) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA277940 |
| SRA |
SRP056074 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66767_CD34_cord_blood.EET.txt.gz |
828.2 Kb |
(ftp)(http) |
TXT |
| GSE66767_U937.EET.txt.gz |
724.8 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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