title: Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.
abstract: In the process of human hematopoiesis, precise regulation of the expression of lineage-specific gene products is critical for multiple cell-fate decisions that govern cell differentiation, proliferation, and self-renewal. Given the important role of microRNAs (miRNAs) in development and differentiation, we examined the global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis and found 49 miRNAs to be differentially expressed, with functional roles in cellular growth and proliferation, and apoptosis. miR-18a was upregulated during erythropoiesis and downregulated during megakaryopoiesis. miR-145 was upregulated during granulopoiesis and down regulated during erythropoiesis. Megakaryopoitic differentiation resulted in significant alteration in the expression of many miRNAs that are believed to play critical roles in the regulation of B and T cell differentiation. Target prediction analyses on three different miRNA databases indicated that TargetScan outperformed microCosm and miRDB in identifying potential miRNA targets associated with hematopoietic differentiation process. An integrated analysis of the observed miRNAs and messenger RNAs (mRNAs) resulted in 87 highly correlated miRNA-mRNA pairs that have major functional roles in cellular growth and proliferation, hematopoietic system development, and Wnt/B-catenin and Flt 3 signaling pathways. We believe that this study will enhance our understanding on the regulatory roles of miRNA in hematopoiesis by providing a library of mRNA-miRNA networks.
authors.affiliation: Genomics Core Facility, Genetics and Development Biology, National Heart, Lung, and Blood Institute, Bethesda, MD, USA; Geriatrics and Clinical Geronotology, National Institutes of Health, Bethesda, MD, USA. Electronic address: Nalini.raghavachari@nih.gov.
authors.forename: Nalini
authors.initials: N
authors.lastname: Raghavachari
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, Bethesda, MD, USA.
authors.forename: Poching
authors.initials: P
authors.lastname: Liu
authors.affiliation: Genomics Core Facility, Genetics and Development Biology, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Barb
authors.affiliation: Genomics Core Facility, Genetics and Development Biology, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Genomics Core Facility, Genetics and Development Biology, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, Bethesda, MD, USA.
authors.forename: Quang Tri
authors.initials: QT
authors.lastname: Nguyen
authors.affiliation: Mathematical and Statistical Computing Laboratory, Center for Information Technology, Bethesda, MD, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D035683:MicroRNAs / Q000032:analysis* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis*; D059467:Transcriptome; D051941:fms-Like Tyrosine Kinase 3 / Q000502:physiology
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3