July 2015

Zebrafish develop system that may improve bone marrow transplant

Zebrafish develop system that may improve bone marrow transplant

Binder, V. (2015). Zebrafish develop system that may improve bone marrow transplant. Boston Children’s Hospital.

 

Nature Cover 23 July 2015

Leonard Zon, MD, Grousbeck Professor of Pediatric Medicine at Harvard Medical School, Investigator at Howard Hughes Medical Institute, Director of the Stem Cell Program, Children’s Hospital Boston, and colleagues have developed a novel competitive marrow transplantation system in adult zebrafish in which engraftment is measured by in vivo fluorescence imaging of the kidney — the adult haematopoietic site.

Using this model to screen for engraftment enhancing activity, the authors identified epoxyeicostrienoic acids, including 11,12-epoxyeicosatrienoic acid (EET), as agents able to enhance engraftment and HSPC specification through the activation of a transcription factor Runx1-mediated expression program. This effect of EET is conserved in mice, indicating possible clinical potential for EET to promote bone marrow transplants.

The findings have been published in the July 23, 2015 issue of Nature. The cover picture of this issue shows two donor fish in red, one in green, and two recipient casper fish with kidneys in red and green to depict chimeric engraftment, as described in their article (photographic work by Vera Binder, MD, Boston Children’s Hospital, graphical work by Ellen van Rooijen, PhD, Boston Children’s Hospital).

Keystone Review

keystone

 

Keystone Symposium on DNA Methylation and Epigenomics – Zebrafish Highlights

March 29 – April 3, 2015

Brandon Kent
Graduate student, Sadler and Walsh laboratories, Icahn School of Medicine at Mount Sinai, USA

Heritable, covalent (“epigenetic”) modification of DNA and the core histone proteins is a central tenet vital to cellular specification, differentiation, and an organism’s development and survival. The join Keystone Symposium on DNA Methylation (http://www.keystonesymposia.org/15Z1) and Epigenomics (March 29th – April 3rd, 2015, Keystone CO) focused on providing the latest insights regarding epigenetic regulation of development, cancer, and application to advanced diagnostics and possible clinical application.

The zebrafish has emerged as a prominent model with regard to studying epigenetic regulation of early embryonic development. Research has been increasingly focused on epigenetic patterning of the zebrafish genome. This joint Keystone Symposium featured work from several prominent zebrafish laboratories.

Members of the Cairns group (University of Utah School of Medicine) presented work regarding epigenetic patterning of the zebrafish zygote to promote the formation of transcriptionally permissive, poised, and repressive domains across the genome in an effort to prime the embryo for proper zygotic genome activation. Work done by the Lister group at the University of Western Australia focused on the role of TET-family proteins in mediating DNA demethylation during development. The Sadler group presented their work on the epigenetic regulator, Uhrf1 and in two posters defined a critical role for this gene in in both the pre-gastrula embryo and at later developmental stages. Most exciting was a workshop previewing the Epigenome Browser (http://epigenomegateway.wustl.edu/browser/) designed by Ting Wang’s group at Washington University in St. Louis. In this comprehensive and user friendly portal to the epigenome, there are datasets of methylation and RNAseq analysis across early embryonic stages and from some adult tissue.

Critically, the zebrafish model system can be utilized to elucidate epigenetic mechanisms underlying embryonic development and cancer, especially in relation to human disease, that other model systems cannot provide. With regard to the high profile and impressive work presented at the Keystone Symposium, the benefits of in vivo modeling in the zebrafish were readily apparent and appreciated.