CBFβ and RUNX1 are required at two different steps during the development of hematopoietic stem cells in zebrafish

Wednesday, September 24, 2014 — Poster Session IV
10:00 a.m. –12:00 p.m.	FAES Academic Center	NHGRI	STEMCELL-1

* FARE Award Winner

Authors

• E. Bresciani
• B. Carrington
• S. Wincovitch
• MP. Jones
• A.V. Gore
• B.M. Weinstein
• R. Sood
• P.P. Liu

Abstract

CBFβ and RUNX1 form a DNA-binding heterodimer and are both required for hematopoietic stem cell (HSC) generation in mice. However, the exact role of CBFβ in the production of HSC remains unclear. Here we generated and characterized two zebrafish cbfb null mutants. The cbfb-/- embryos underwent primitive hematopoiesis and developed transient erythromyeloid progenitors, but they lacked definitive hematopoiesis. Unlike runx1 mutants in which HSCs are not formed, nascent, runx1+/c-myb+ HSCs were formed in cbfb-/- embryos. However, the nascent HSCs were not released from the aorta-gonad-mesonephros (AGM) region, as evidenced by the accumulation of runx1+ cells in the AGM that could not enter circulation. Moreover, wild type embryos treated with an inhibitor of RUNX1-CBFβ interaction, Ro5-3335, phenocopied the hematopoietic defects in cbfb-/- mutants, rather than those in runx1-/- mutants. Finally, we found that cbfb was downstream of the Notch pathway during HSC development. Our data suggest that runx1 and cbfb are required at two different steps during early HSC development. CBFβ is not required for nascent HSC emergence but is required for the release of HSCs from AGM into circulation. Our results also indicate that RUNX1 can drive the emergence of nascent HSCs in the AGM without its heterodimeric partner CBFβ.

back to top