PUBLICATION

The Spliceosomal Component Sf3b1 is Essential for Hematopoietic Differentiation in Zebrafish

Authors
De La Garza, A., Cameron, R.C., Nik, S., Payne, S.G., Bowman, T.V.
ID
ZDB-PUB-160605-2
Date
2016
Source
Experimental hematology   44(9): 826-837.e4 (Journal)
Registered Authors
Bowman, Teresa
Keywords
none
MeSH Terms
  • Hematopoiesis/genetics*
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Receptors, Notch/metabolism
  • Cell Differentiation/genetics*
  • Biomarkers
  • Erythroid Cells/cytology
  • Erythroid Cells/metabolism
  • Animals
  • Apoptosis/genetics
  • Mutation
  • Signal Transduction
  • Hematopoietic Stem Cells/cytology*
  • Hematopoietic Stem Cells/metabolism*
  • RNA Splicing Factors/genetics*
  • Myeloid Cells/cytology
  • Myeloid Cells/metabolism
  • Zebrafish Proteins/genetics*
(all 18)
PubMed
27260753 Full text @ Exp. Hematol.
Abstract
SF3B1 (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.
Genes / Markers
Figures
No images available
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
WT + MO2-sf3b1standard conditionsPrim-5
WT + MO2-sf3b1standard conditionsPrim-5
WT + MO2-sf3b1standard conditionsLong-pec
WT + MO2-sf3b1standard conditionsLong-pec
sf3b1hi3394aTg/hi3394aTgstandard conditions10-13 somites
sf3b1hi3394aTg/hi3394aTgstandard conditions26+ somites
sf3b1hi3394aTg/hi3394aTgstandard conditions26+ somites
sf3b1hi3394aTg/hi3394aTgstandard conditionsPrim-5
sf3b1hi3394aTg/hi3394aTgstandard conditionsPrim-5
sf3b1hi3394aTg/hi3394aTgstandard conditionsPrim-5
1 - 10 of 27
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hi3394aTgTransgenic Insertion
la781TgTransgenic Insertion
    nz50TgTransgenic Insertion
      pd27TgTransgenic Insertion
        um14TgTransgenic Insertion
          zf169TgTransgenic Insertion
            1 - 6 of 6
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            Human Disease / Model
            No data available
            Sequence Targeting Reagents
            Target Reagent Reagent Type
            sf3b1MO2-sf3b1MRPHLNO
            1 - 1 of 1
            Show
            Fish
            Fish
            la781Tg
            nz50Tg
            sf3b1hi3394aTg/hi3394aTg
            sf3b1hi3394aTg/hi3394aTg; la781Tg
            sf3b1hi3394aTg/hi3394aTg; nz50Tg
            sf3b1hi3394aTg/hi3394aTg; pd27Tg; zf169Tg
            sf3b1hi3394aTg/hi3394aTg; um14Tg
            um14Tg
            WT
            WT + MO2-sf3b1
            1 - 10 of 10
            Show
            Antibodies
            No data available
            Orthology
            Engineered Foreign Genes
            Marker Marker Type Name
            DsRed2EFGDsRed2
            EGFPEFGEGFP
            GFPEFGGFP
            1 - 3 of 3
            Show
            Mapping
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            Citation
            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.