|ZFIN ID: ZDB-PUB-160605-2|
The Spliceosomal Component Sf3b1 is Essential for Hematopoietic Differentiation in Zebrafish
De La Garza, A., Cameron, R.C., Nik, S., Payne, S.G., Bowman, T.V.
|Source:||Experimental hematology 44(9): 826-837.e4 (Journal)|
|Registered Authors:||Bowman, Teresa|
|PubMed:||27260753 Full text @ Exp. Hematol.|
De La Garza, A., Cameron, R.C., Nik, S., Payne, S.G., Bowman, T.V. (2016) The Spliceosomal Component Sf3b1 is Essential for Hematopoietic Differentiation in Zebrafish. Experimental hematology. 44(9):826-837.e4.
ABSTRACTSF3B1 (Splicing factor 3b, subunit 1) is one of the most commonly mutated factors in myelodysplastic syndrome (MDS). Although the genetic correlation between SF3B1 mutations and MDS etiology are quite strong, no in vivo model currently exists to explore how SF3B1 loss alters blood cell development. Using zebrafish mutants, we show that proper function of Sf3b1 is required for all hematopoietic lineages. Similar to MDS patients, zebrafish sf3b1 mutants develop a macrocytic anemia-like phenotype due to a block in maturation at a late progenitor stage. The mutant embryos also develop neutropenia as their primitive myeloid cells fail to mature and turn on differentiation markers such as l-plastin and myeloperoxidase. In contrast, production of definitive hematopoietic stem and progenitor cells (HSPCs) from hemogenic endothelial cells within the dorsal aorta is greatly diminished, while arterial endothelial cells are correctly fated. Notch signaling, imperative for the endothelial-to-hematopoietic transition, is also normal, indicating HSPC induction is blocked in sf3b1 mutants downstream or independent of Notch signaling. The data demonstrate Sf3b1 function is necessary during key differentiation fate decisions in multiple blood cell types. Zebrafish sf3b1 mutants offer a novel animal model to explore the role of splicing in hematopoietic development and provide an excellent in vivo system to delve into the why and how Sf3b1 dysfunction is detrimental to hematopoietic differentiation, which could enlighten MDS diagnosis and treatment.