title: Global transcriptome analyses of human and murine terminal erythroid differentiation.
abstract: We recently developed fluorescence-activated cell sorting (FACS)-based methods to purify morphologically and functionally discrete populations of cells, each representing specific stages of terminal erythroid differentiation. We used these techniques to obtain pure populations of both human and murine erythroblasts at distinct developmental stages. RNA was prepared from these cells and subjected to RNA sequencing analyses, creating unbiased, stage-specific transcriptomes. Tight clustering of transcriptomes from differing stages, even between biologically different replicates, validated the utility of the FACS-based assays. Bioinformatic analyses revealed that there were marked differences between differentiation stages, with both shared and dissimilar gene expression profiles defining each stage within transcriptional space. There were vast temporal changes in gene expression across the differentiation stages, with each stage exhibiting unique transcriptomes. Clustering and network analyses revealed that varying stage-specific patterns of expression observed across differentiation were enriched for genes of differing function. Numerous differences were present between human and murine transcriptomes, with significant variation in the global patterns of gene expression. These data provide a significant resource for studies of normal and perturbed erythropoiesis, allowing a deeper understanding of mechanisms of erythroid development in various inherited and acquired erythroid disorders.
authors.affiliation: Laboratory of Membrane Biology and Red Cell Physiology Laboratory, New York Blood Center, New York, NY; College of Life Science, Zhengzhou University, Zhengzhou, Henan, China;
authors.forename: Xiuli
authors.initials: X
authors.lastname: An
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT;
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Schulz
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY;
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY; Molecular Biology Research Center, School of Biological Science and Technology and State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China; and.
authors.forename: Kunlu
authors.initials: K
authors.lastname: Wu
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY; Molecular Biology Research Center, School of Biological Science and Technology and State Key Laboratory of Medical Genetics of China, Central South University, Changsha, Hunan, China; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Laboratory of Membrane Biology and.
authors.forename: Fumin
authors.initials: F
authors.lastname: Xue
authors.affiliation: Laboratory of Membrane Biology and.
authors.forename: Jingping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Red Cell Physiology Laboratory, New York Blood Center, New York, NY;
authors.forename: Narla
authors.initials: N
authors.lastname: Mohandas
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT; Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, CT.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Gallagher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D016000:Cluster Analysis; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism*; D004920:Erythropoiesis / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D051379:Mice; D017423:Sequence Analysis, RNA; D014157:Transcription Factors / Q000235:genetics; D059467:Transcriptome
chemical_list: D014157:Transcription Factors