PUBLICATION

Essential Role of RIG-I in Hematopoietic Precursor Emergence in Primitive Hematopoiesis during Zebrafish Development

Authors
Wang, Y.Y., Nie, L., Xu, X.X., Shao, T., Fan, D.D., Lin, A.F., Xiang, L.X., Shao, J.Z.
ID
ZDB-PUB-220520-14
Date
2022
Source
ImmunoHorizons   6: 283-298 (Journal)
Registered Authors
Fan, Dongdong, Lin, Aifu, Shao, Jian-zhong, Shao, Tong, Wang, Yueyi, Xiang, Lixin
Keywords
none
MeSH Terms
  • Animals
  • RNA
  • Hematopoiesis/genetics
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
  • Embryonic Development
  • Zebrafish*/genetics
(all 7)
PubMed
35589132 Full text @ Immunohorizons
Abstract
Retinoic acid-inducible gene I (RIG-I) is an important cytosolic pattern recognition receptor crucial for sensing RNA virus infection and initiating innate immune responses. However, the participation of RIG-I in cellular development under physiological conditions remains limited. In this study, the regulatory role of RIG-I in embryonic hematopoiesis was explored in a zebrafish model. Results showed that rig-I was ubiquitously expressed during embryogenesis at 24 h postfertilization (hpf). A defect in RIG-I remarkably disrupted the emergence of primitive hematopoietic precursors and subsequent myeloid and erythroid lineages. In contrast, RIG-I deficiency did not have an influence on the generation of endothelial precursors and angiogenesis and the development of mesoderm and adjacent tissues. The alteration in these phenotypes was confirmed by whole-mount in situ hybridization with lineage-specific markers. In addition, immunostaining and TUNEL assays excluded the abnormal proliferation and apoptosis of hematopoietic precursors in RIG-I-deficient embryos. Mechanistically, RIG-I regulates primitive hematopoiesis through downstream IFN signaling pathways, as shown by the decline in ifnφ2 and ifnφ3 expression, along with rig-I knockdown, and rescue of the defects of hematopoietic precursors in RIG-I-defective embryos after administration with ifnφ2 and ifnφ3 mRNAs. Additionally, the defects of hematopoietic precursors in RIG-I morphants could be efficiently rescued by the wild-type RIG-I but could not be restored by the RNA-binding-defective RIG-I with site mutations at the RNA-binding pocket, which are essential for association with RNAs. This finding suggested that endogenous RNAs may serve as agonists to activate RIG-I-modulated primitive hematopoiesis. This study revealed the functional diversity of RIG-I under physiological conditions far beyond that previously known.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
zju303
    Small Deletion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    rigiCRISPR2-rigiCRISPR
    rigiMO2-rigiMRPHLNO
    1 - 2 of 2
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    Fish
    1 - 3 of 3
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    No data available
    Mapping
    No data available