Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing.
Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing.
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通过深度测序评估 Diamond-Blackfan 贫血斑马鱼模型中 Rpl11 缺陷导致的造血功能衰竭
DOI：
10.1186/1471-2164-14-896
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发表时间：
2013-12-17
期刊：
影响因子：
4.4
通讯作者：
Fang X
中科院分区：
文献类型：
--
作者：
Zhang Z;Jia H;Zhang Q;Wan Y;Zhou Y;Jia Q;Zhang W;Yuan W;Cheng T;Zhu X;Fang X
Diamond-Blackfan贫血是一种罕见的先天性红细胞发育不良，在出生后不久就会发生。RPL 11突变占造血表型缺陷的人DBA病例的约4.8%。然而，RPL 11调节DBA造血的机制仍然难以捉摸。在这项研究中，我们使用Rpl 11缺陷斑马鱼模型的深度测序数据分析了转录组，以确定Rpl 11介导的造血功能衰竭并研究其潜在机制。我们通过鉴定受影响的血液学基因、造血相关通路和调控网络来表征Rpl 11缺陷斑马鱼胚胎的血液学缺陷。我们发现Rpl 11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的失调有关，这些基因包括tfa、tfr 1b、alas 2和slc 25 a37，它们参与血红素和血红蛋白的生物合成。此外，我们发现造血干细胞（HSC）标记物cmyb和HSC转录因子tal 1和hoxb 4a在Rpl 11缺陷的斑马鱼胚胎中的表达减少，表明造血缺陷可能与受损的HSC形成、分化和增殖有关。然而，Rpl 11缺乏并不影响其他血细胞谱系如粒细胞和髓细胞的发育。我们使用转录组深度测序鉴定了Rpl 11缺陷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，Rpl 11缺陷型斑马鱼可以作为DBA的模型，并可能提供深入了解突变型RPL 11介导的人类DBA疾病的发病机制。
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. 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. 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.
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影响因子：
3.9
作者：
Boria, Ilenia;Garelli, Emanuela;Gazda, Hanna T.;Aspesi, Anna;Quarello, Paola;Pavesi, Elisa;Ferrante, Daniela;Meerpohl, Joerg J.;Kartal, Mutlu;Da Costa, Lydie;Proust, Alexis;Leblanc, Thierry;Simansour, Maud;Dahl, Niklas;Froejmark, Anne-Sophie;Pospisilova, Dagmar;Cmejla, Radek;Beggs, Alan H.;Sheen, Mee R.;Landowski, Michael;Buros, Christopher M.;Clinton, Catherine M.;Dobson, Lori J.;Vlachos, Adrianna;Atsidaftos, Eva;Lipton, Jeffrey M.;Ellis, Steven R.;Ramenghi, Ugo;Dianzani, Irma
通讯作者：
Dianzani, Irma
影响因子：
6.5
作者：
Danilova N;Sakamoto KM;Lin S
通讯作者：
Lin S
影响因子：
1.7
作者：
Da Costa, L.;Moniz, H.;Simansour, M.;Tchernia, G.;Mohandas, N.;Leblanc, T.
通讯作者：
Leblanc, T.
影响因子：
4.8
作者：
Ferreira, C;Bucchini, D;Beaumont, C
通讯作者：
Beaumont, C
影响因子：
10.5
作者：
Fleming, MD;Campagna, DR;Andrews, NC
通讯作者：
Andrews, NC