title: MiR-24 is required for hematopoietic differentiation of mouse embryonic stem cells.
abstract: Overexpression of miRNA, miR-24, in mouse hematopoietic progenitors increases monocytic/ granulocytic differentiation and inhibits B cell development. To determine if endogenous miR-24 is required for hematopoiesis, we antagonized miR-24 in mouse embryonic stem cells (ESCs) and performed in vitro differentiations. Suppression of miR-24 resulted in an inability to produce blood and hematopoietic progenitors (HPCs) from ESCs. The phenotype is not a general defect in mesoderm production since we observe production of nascent mesoderm as well as mesoderm derived cardiac muscle and endothelial cells. Results from blast colony forming cell (BL-CFC) assays demonstrate that miR-24 is not required for generation of the hemangioblast, the mesoderm progenitor that gives rise to blood and endothelial cells. However, expression of the transcription factors Runx1 and Scl is greatly reduced, suggesting an impaired ability of the hemangioblast to differentiate. Lastly, we observed that known miR-24 target, Trib3, is upregulated in the miR-24 antagonized embryoid bodies (EBs). Overexpression of Trib3 alone in ESCs was able to decrease HPC production, though not as great as seen with miR-24 knockdown. These results demonstrate an essential role for miR-24 in the hematopoietic differentiation of ESCs. Although many miRNAs have been implicated in regulation of hematopoiesis, this is the first miRNA observed to be required for the specification of mammalian blood progenitors from early mesoderm.
authors: Harper Cancer Research Institute, South Bend, Indiana, United States of America; Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors: Lynn
authors: L
authors: Roy
authors: Harper Cancer Research Institute, South Bend, Indiana, United States of America; Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors: Emmanuel
authors: E
authors: Bikorimana
authors: Dept. of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors: Danica
authors: D
authors: Lapid
authors: Dept. of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors: Hyewon
authors: H
authors: Choi
authors: Harper Cancer Research Institute, South Bend, Indiana, United States of America; Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America.
authors: Tan
authors: T
authors: Nguyen
authors: Harper Cancer Research Institute, South Bend, Indiana, United States of America; Microbiology and Immunology, Indiana University School of Medicine, South Bend, Indiana, United States of America; Dept. of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United States of America.
authors: Richard
authors: R
authors: Dahl
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000235:genetics*; D003114:Colony-Forming Units Assay; D050676:Core Binding Factor Alpha 2 Subunit / Q000096:biosynthesis; D004622:Embryo, Mammalian; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D050676:Core Binding Factor Alpha 2 Subunit; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C529080:Mirn24 microRNA, mouse; C493726:Runx1 protein, mouse; C474830:TRB3 protein, mouse; C489366:Tal1 protein, mouse
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