Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment

Pulin Li, Jamie L. Lahvic, Vera Binder, Emily K. Pugach, Elizabeth B. Riley, Owen J. Tamplin, Dipak Panigrahy, Teresa V. Bowman, Francesca G. Barrett, Garrett C. Heffner, Shannon McKinney-Freeman, Thorsten M. Schlaeger, George Q. Daley, Darryl C. Zeldin, Leonard I. Zon

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 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)Kγ. 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.

Original languageEnglish (US)
Pages (from-to)468-471
Number of pages4
JournalNature
Volume523
Issue number7561
DOIs
StatePublished - Jul 22 2015
Externally publishedYes

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Hematopoiesis
Hematopoietic Stem Cells
Bone Marrow
Acids
Transcription Factor AP-1
Zebrafish
Transplants
Fetal Blood
Phosphatidylinositol 3-Kinases
Endothelium
Regeneration
Mammals
Leukemia
Embryonic Structures

ASJC Scopus subject areas

  • General
  • Medicine(all)

Cite this

Li, P., Lahvic, J. L., Binder, V., Pugach, E. K., Riley, E. B., Tamplin, O. J., ... Zon, L. I. (2015). Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature, 523(7561), 468-471. https://doi.org/10.1038/nature14569

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.

In: Nature, Vol. 523, No. 7561, 22.07.2015, p. 468-471.

Research output: Contribution to journalArticle

Li, P, Lahvic, JL, Binder, V, Pugach, EK, Riley, EB, Tamplin, OJ, Panigrahy, D, Bowman, TV, Barrett, FG, Heffner, GC, McKinney-Freeman, S, Schlaeger, TM, Daley, GQ, Zeldin, DC & Zon, LI 2015, 'Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment', Nature, vol. 523, no. 7561, pp. 468-471. https://doi.org/10.1038/nature14569
Li P, Lahvic JL, Binder V, Pugach EK, Riley EB, Tamplin OJ et al. Epoxyeicosatrienoic acids enhance embryonic haematopoiesis and adult marrow engraftment. Nature. 2015 Jul 22;523(7561):468-471. https://doi.org/10.1038/nature14569
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. In: Nature. 2015 ; Vol. 523, No. 7561. pp. 468-471.
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