title: Assessment of hematopoietic failure due to Rpl11 deficiency in a zebrafish model of Diamond-Blackfan anemia by deep sequencing.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Haibo
authors.initials: H
authors.lastname: Jia
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Wan
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qiong
authors.initials: Q
authors.lastname: Jia
authors.forename: Wanguang
authors.initials: W
authors.lastname: Zhang
authors.forename: Weiping
authors.initials: W
authors.lastname: Yuan
authors.forename: Tao
authors.initials: T
authors.lastname: Cheng
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China. zhuxf6465@gmail.com.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Fang
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D016000:Cluster Analysis; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000473:pathology; D053263:Gene Regulatory Networks; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006454:Hemoglobins / Q000096:biosynthesis; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007501:Iron / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics*; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D059467:Transcriptome; D015027:Zebrafish
chemical_list: D006454:Hemoglobins; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; D007501:Iron