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Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment
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 transpla...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754787/ https://www.ncbi.nlm.nih.gov/pubmed/26201599 http://dx.doi.org/10.1038/nature14569 |
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author | Li, Pulin Lahvic, Jamie L. Binder, Vera Pugach, Emily K. Riley, Elizabeth B. Tamplin, Owen J. Panigrahy, Dipak Bowman, Teresa V. Barrett, Francesca G. Heffner, Garrett C. McKinney-Freeman, Shannon Schlaeger, Thorsten M. Daley, George Q. Zeldin, Darryl C. Zon, Leonard I. |
author_facet | Li, Pulin Lahvic, Jamie L. Binder, Vera Pugach, Emily K. Riley, Elizabeth B. Tamplin, Owen J. Panigrahy, Dipak Bowman, Teresa V. Barrett, Francesca G. Heffner, Garrett C. McKinney-Freeman, Shannon Schlaeger, Thorsten M. Daley, George Q. Zeldin, Darryl C. Zon, Leonard I. |
author_sort | Li, Pulin |
collection | PubMed |
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(1,2) that enhance HSPC engraftment. EETs’ pro-haematopoietic effects were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the PI3K pathway, specifically PI3Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate 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. |
format | Online Article Text |
id | pubmed-4754787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-47547872016-02-16 Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment Li, Pulin Lahvic, Jamie L. Binder, Vera Pugach, Emily K. Riley, Elizabeth B. Tamplin, Owen J. Panigrahy, Dipak Bowman, Teresa V. Barrett, Francesca G. Heffner, Garrett C. McKinney-Freeman, Shannon Schlaeger, Thorsten M. Daley, George Q. Zeldin, Darryl C. Zon, Leonard I. Nature Article 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(1,2) that enhance HSPC engraftment. EETs’ pro-haematopoietic effects were conserved in the developing zebrafish embryo, where 11,12-EET promoted HSPC specification by activating a unique AP-1/runx1 transcription program autonomous to the haemogenic endothelium. This effect required the activation of the PI3K pathway, specifically PI3Kγ. In adult HSPCs, 11,12-EET induced transcriptional programs, including AP-1 activation, which modulate 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. 2015-07-23 /pmc/articles/PMC4754787/ /pubmed/26201599 http://dx.doi.org/10.1038/nature14569 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Li, Pulin Lahvic, Jamie L. Binder, Vera Pugach, Emily K. Riley, Elizabeth B. Tamplin, Owen J. Panigrahy, Dipak Bowman, Teresa V. Barrett, Francesca G. Heffner, Garrett C. McKinney-Freeman, Shannon Schlaeger, Thorsten M. Daley, George Q. Zeldin, Darryl C. Zon, Leonard I. Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title | Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title_full | Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title_fullStr | Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title_full_unstemmed | Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title_short | Epoxyeicosatrienoic Acids Enhance Embryonic Haematopoiesis and Adult Marrow Engraftment |
title_sort | epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754787/ https://www.ncbi.nlm.nih.gov/pubmed/26201599 http://dx.doi.org/10.1038/nature14569 |
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