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首页> 外文期刊>BMC Genomics >Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing
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Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing

机译：通过深度测序评估在钻石-布莱克范贫血的斑马鱼模型中由于Rpl11缺乏引起的造血功能衰竭

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Background Diamond–Blackfan anemia is a rare congenital red blood cell dysplasia that develops soon after birth. RPL11 mutations account for approximately 4.8% of human DBA cases with defective hematopoietic phenotypes. However, the mechanisms by which RPL11 regulates hematopoiesis in DBA remain elusive. In this study, we analyzed the transcriptome using deep sequencing data from an Rpl11-deficient zebrafish model to identify Rpl11-mediated hematopoietic failure and investigate the underlying mechanisms. Results We characterized hematological defects in Rpl11-deficient zebrafish embryos by identifying affected hematological genes, hematopoiesis-associated pathways, and regulatory networks. We found that hemoglobin biosynthetic and hematological defects in Rpl11-deficient zebrafish were related to dysregulation of iron metabolism-related genes, including tfa, tfr1b, alas2 and slc25a37, which are involved in heme and hemoglobin biosynthesis. In addition, we found reduced expression of the hematopoietic stem cells (HSC) marker cmyb and HSC transcription factors tal1 and hoxb4a in Rpl11-deficient zebrafish embryos, indicating that the hematopoietic defects may be related to impaired HSC formation, differentiation, and proliferation. However, Rpl11 deficiency did not affect the development of other blood cell lineages such as granulocytes and myelocytes. Conclusion We identified hematopoietic failure of Rpl11-deficient zebrafish embryos using transcriptome deep sequencing and elucidated potential underlying mechanisms. The present analyses demonstrate that Rpl11-deficient zebrafish may serve as a model of DBA and may provide insights into the pathogenesis of mutant RPL11-mediated human DBA disease.
机译：背景钻石-布莱克范贫血是一种罕见的先天性红细胞发育异常，在出生后不久就会发展。 RPL11突变约占造血表型缺陷的人类DBA病例的4.8％。但是，RPL11调节DBA中的造血作用的机制仍然难以捉摸。在这项研究中，我们使用来自Rpl11缺陷斑马鱼模型的深度测序数据分析了转录组，以鉴定Rpl11介导的造血功能衰竭并研究其潜在机制。结果我们通过鉴定受影响的血液基因，造血相关途径和调节网络来鉴定Rpl11缺陷型斑马鱼胚胎中的血液学缺陷。我们发现，Rpl11缺陷斑马鱼的血红蛋白生物合成和血液学缺陷与铁代谢相关基因（包括tfa，tfr1b，alas2和slc25a37）的异常调节有关，这些基因参与血红素和血红蛋白的生物合成。此外，我们发现Rpl11缺陷的斑马鱼胚胎中造血干细胞（HSC）标记cmyb和HSC转录因子tal1和hoxb4a的表达降低，表明造血缺陷可能与HSC形成，分化和增殖受损有关。但是，Rpl11缺乏并不影响其他血细胞谱系的发展，例如粒细胞和骨髓细胞。结论我们使用转录组深度测序鉴定了Rpl11缺陷型斑马鱼胚胎的造血功能衰竭，并阐明了潜在的潜在机制。目前的分析表明，缺乏Rpl11的斑马鱼可作为DBA的模型，并可为突变RPL11介导的人DBA疾病的发病机理提供见解。

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