Epoxyeicosatrienoic Acids Enhance Haematopoietic Stem and Progenitor Cell Specification and Engraftment
Transcriptomics Dataset
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| Accession | GSE66767 |
| Title | Epoxyeicosatrienoic Acids Enhance Haematopoietic Stem and Progenitor Cell Specification and Engraftment |
| Description | 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. |
| Landing Page | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE66767 |
| Repository | Gene Expression Omnibus |
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