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Cited by 19Blood disorders and treatmentsZebrafish Biomedical Research ApplicationsHematopoietic Stem Cell Transplantation

The nuclear gene rpl18 regulates erythroid maturation via JAK2-STAT3 signaling in zebrafish model of Diamond–Blackfan anemia

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Chen, Cheng, Lu, Mengjia, Lin, Shuo, Qin, Wei·2020·Cell Death & Disease
DOI 10.1038/s41419-020-2331-5PMC PMC7031319
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Abstract

Diamond–Blackfan anemia (DBA) is a rare, inherited bone marrow failure syndrome, characterized by red blood cell aplasia, developmental abnormalities, and enhanced risk of malignancy. However, the underlying pathogenesis of DBA is yet to be understood. Recently, mutations in the gene encoding ribosomal protein (RP) L18 were identified in DBA patients. RPL18 is a crucial component of the ribosomal large subunit but its role in hematopoiesis remains unknown. To genetically model the ribosomal defect identified in DBA, we generated a rpl18 mutant line in zebrafish, using CRISPR/Cas9 system. Molecular characterization of this mutant line demonstrated that Rpl18 deficiency mirrored the erythroid defects of DBA, namely a lack of mature red blood cells. Rpl18 deficiency caused an increase in p53 activation and JAK2-STAT3 activity. Furthermore, we found inhibitors of JAK2 or STAT3 phosphorylation could rescue anemia in rpl18 mutants. Our research provides a new in vivo model of Rpl18 deficiency and suggests involvement of signal pathway of JAK2-STAT3 in the DBA pathogenesis.

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  • The widespread reduction in translation gene expression suggests a pathological mechanism similar to Diamond-Blackfan anemia (DBA).

    “suggesting a pathological mechanism similar to that of Diamond-Blackfan anemia (DBA), a disorder associated with insufficient expression of ribosome-related genes, such as rps19, rps24, and rps17 (Chen et al., 2020; Doherty et al., 2010).”

    From Deciphering the toxic effects of polystyrene nanoparticles on erythropoiesis at single-cell resolution (2025) · cites this paper as Chen et al., 2020

    The Introduction (page unavailable) identifies ribosomal-protein haploinsufficiency as a major cause of DBA, supporting the proposed similarity. The Results section on transcriptome analysis (page unavailable) reports disrupted ribosome biogenesis and altered ribosome-related gene expression in rpl18-mutant zebrafish. It does not establish a widespread reduction in translation-gene expression or identify rps24 and rps17 as examples. (LLM, conf=0.83)

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Research works printed but not linked: 33

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Cited by

Sorted by citations

Authors
Chen, C., Lu, M., Lin, S., & Qin, W.
Affiliations
  • Peking University (CN)
  • University of California, Los Angeles (US)
Corresponding author
Qin, Wei
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2020-02-19
Volume
11
Issue
2
Pages
135-135
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-020-2331-5
PMC
PMC7031319
OpenAlex
W3008860704
Cited by
19
References
2
Citations by year
2026: 3 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 1
FWCI
1.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (31801209)
  • Shenzhen Science and Technology Innovation Commission (JCYJ20180302153633991)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
Diamond-Blackfan anemia, ribosomal protein L18, erythroid maturation, JAK2/STAT3 signaling, p53 activation, zebrafish mutant model, CRISPR/Cas9 mutagenesis, hematopoiesis
MeSH terms
Animals, Disease Models, Animal, Erythropoiesis, Phosphorylation, Ribosomal Proteins, Zebrafish, Signal Transduction, Tumor Suppressor Protein p53, Anemia, Diamond-Blackfan, Zebrafish Proteins, Animals, Genetically Modified, Erythroid Cells, Protein Kinase Inhibitors, STAT3 Transcription Factor, Janus Kinase 2

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