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

Chen, Cheng; Lu, Mengjia; Lin, Shuo; Qin, Wenzhi

doi:10.1038/s41419-020-2331-5

Cited by 12 publications

(14 citation statements)

References 37 publications

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“…1f, g ). Our previous study demonstrated that loss of ribosomal protein (RP) genes in zebrafish often results in a small head, small eyes, and enlarged hindbrain ventricles 20 , 21 . The same phenotype was observed in rpl17 -NGA PAM knockout F0 embryos (Fig.…”

Section: Resultsmentioning

confidence: 99%

SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish

Liang

Yang

et al. 2022

Nat Commun

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Precise genetic modifications in model organisms are essential for biomedical research. The recent development of PAM-less base editors makes it possible to assess the functional impact and pathogenicity of nucleotide mutations in animals. Here we first optimize SpG and SpRY systems in zebrafish by purifying protein combined with synthetically modified gRNA. SpG shows high editing efficiency at NGN PAM sites, whereas SpRY efficiently edit PAM-less sites in the zebrafish genome. Then, we generate the SpRY-mediated cytosine base editor SpRY-CBE4max and SpRY-mediated adenine base editor zSpRY-ABE8e. Both target relaxed PAM with up to 96% editing efficiency and high product purity. With these tools, some previously inaccessible disease-relevant genetic variants are generated in zebrafish, supporting the utility of high-resolution targeting across genome-editing applications. Our study significantly improves CRISPR-Cas targeting in the genomic landscape of zebrafish, promoting the application of this model organism in revealing gene function, physiological mechanisms, and disease pathogenesis.

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Section: Resultsmentioning

confidence: 99%

SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish

Liang

Yang

et al. 2022

Nat Commun

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“…Rpl18 is an important component of the large subunit of ribosome and plays an important role in ribosome assembly. C Chen [ 39 ] reported that Rpl18 regulates erythroid maturation via JAK2/STAT3 signaling. Loh JT [ 40 ] demonstrated that suppressing JAK2/STAT3 signaling in neutrophils was important for intestinal homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Experimental Evidence of Buyang Huanwu Decoction and Related Modern Preparations (Naoxintong Capsule and Yangyin Tongnao Granule) in Treating Cerebral Ischemia: Intestinal Microorganisms and Transcriptomics in Rats

Yin

Yang

Zhao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. The traditional Chinese medicines of Buyang Huanwu decoction (BYHW), Naoxintong capsule (NXT), and Yangyin Tongnao granules (YYTN) have excellent effects in preventing and treating cerebrovascular disease and are widely tolerated by patients. However, their effects on middle cerebral artery occlusion (MCAO) remain unknown. Methods. We evaluated gut microbiota alterations, the brain transcriptome, and nerve cell responses in rats with MCAO. Results. Our results showed that BYHW, NXT, and YYTN not only effectively improved the damaged state of blood vessels in rats and restored nerve function, but also improved survival. Additional experiments showed that treatment with BYHW, NXT, and YYTN regulated the intestinal microflora. Transcriptome analyses showed that BYHW, NXT, and YYTN modulated the transcriptome of rats with MCAO. The common mechanism of the three prescriptions for the treatment of cerebral ischemia may be related to the intestinal flora regulation of 60S ribosomal protein L18 (Rpl18), eukaryotic translation initiation factor 3 subunit, Ras homolog family member C, G protein subunit gamma 13 (Gng13), and Gng10 genes, among which Rpl18 is the most important. In addition, the three prescriptions had great specificity as anticerebral ischemia targets. Moreover, BYHW, NXT, and YYTN mitigated MCAO-induced hyperactivation of microglia and astrocytes. Conclusion. This study provides a foundation for further research on the mechanisms and treatment of IS. The results strongly suggest that key gut microbiota can be used to study functional genomics of brain, leading to novel discoveries about key genes involved in important biological processes.

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“…Due to the nature of the genetic defects, this proinflammatory innate immune response could indeed be attributed to endogenous factors, such as aberrant RNA components resulting from disrupted ribosome assembly. Whether inflammatory signaling is a side effect or an integral part of the pathogenic mechanism in DBA models has been addressed in a more recent rpl18 zebrafish mutant study ( Chen et al, 2020 ). Like multiple other ribosomopathy zebrafish models, rpl18 mutants activate p53 and JAK-STAT pathways.…”

Section: Ribosomopathies Cytopenias and Inflammatory Signalingmentioning

confidence: 99%

Zebrafish models of inflammation in hematopoietic development and disease

Ketharnathan

Rajan

Prykhozhij

et al. 2022

Front. Cell Dev. Biol.

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Zebrafish offer an excellent tool for studying the vertebrate hematopoietic system thanks to a highly conserved and rapidly developing hematopoietic program, genetic amenability, optical transparency, and experimental accessibility. Zebrafish studies have contributed to our understanding of hematopoiesis, a complex process regulated by signaling cues, inflammation being crucial among them. Hematopoietic stem cells (HSCs) are multipotent cells producing all the functional blood cells, including immune cells. HSCs respond to inflammation during infection and malignancy by proliferating and producing the blood cells in demand for a specific scenario. We first focus on how inflammation plays a crucial part in steady-state HSC development and describe the critical role of the inflammasome complex in regulating HSC expansion and balanced lineage production. Next, we review zebrafish studies of inflammatory innate immune mechanisms focusing on interferon signaling and the downstream JAK-STAT pathway. We also highlight insights gained from zebrafish models harbouring genetic perturbations in the role of inflammation in hematopoietic disorders such as bone marrow failure, myelodysplastic syndrome, and myeloid leukemia. Indeed, inflammation has been recently identified as a potential driver of clonal hematopoiesis and leukemogenesis, where cells acquire somatic mutations that provide a proliferative advantage in the presence of inflammation. Important insights in this area come from mutant zebrafish studies showing that hematopoietic differentiation can be compromised by epigenetic dysregulation and the aberrant induction of signaling pathways.

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

Cited by 12 publications

References 37 publications

SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish

SpG and SpRY variants expand the CRISPR toolbox for genome editing in zebrafish

Experimental Evidence of Buyang Huanwu Decoction and Related Modern Preparations (Naoxintong Capsule and Yangyin Tongnao Granule) in Treating Cerebral Ischemia: Intestinal Microorganisms and Transcriptomics in Rats

Zebrafish models of inflammation in hematopoietic development and disease

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