Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Thrombocythemic Platelets microRNA Profiling

ABSTRACT: Post-transcriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biological processes and disease. We systematically dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and healthy controls, and integrated these data with transcriptomic and proteomic platforms. We identified and validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a discrete 3-member subset effectively defines ET phenotypes. The genetic signature includes functional guide and passenger strands of the previously-uncharacterized miR 490 (5p and 3p), both of which displayed restricted, low-level expression in megakaryocytes/platelets (compared to leukocytes), and aberrant expression during thrombocytosis, most profound in essential thrombocythemia (ET). Overexpression of miR 490 in a bilineage differentiation model of megakaryocyte/erythroid progenitor formation was insufficient for hematopoietic stem cell colony differentiation and/or lineage specification. Systematic integration of transcriptomic and mass spectrometric datasets with functional reporter assays identified dishevelled associated activator of morphogenesis 1 (DAAM1) as a unique miR 490 5p protein target demonstrating decreased expression in ET platelets, putatively modulated by translational control (and not by mRNA target degradation). Our data define a dysregulated miRNA fingerprint in thrombocytosis, and collectively support a developmentally-restricted function of miR 490 (and its putative DAAM1 target) to conditions associated with exaggerated megakaryocytopoiesis and/or proplatelet formation. Human platelets from a total of 79 samples in 3 phenotypic groups: essential thrombocythemia (ET, N =27), reactive thrombocytosis (RT, N=22) and healthy controls (NO, N=30) were measured on array platform

ORGANISM(S): Homo sapiens

SUBMITTER: Xiao Xu

PROVIDER: E-GEOD-39046 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

Xu Xiao X Gnatenko Dmitri V DV Ju Jingfang J Hitchcock Ian S IS Martin Dwight W DW Zhu Wei W Bahou Wadie F WF

Blood 20120806 17

Posttranscriptional and translational controls mediated by microRNAs (miRNA) regulate diverse biologic processes. We dissected regulatory effects of miRNAs relevant to megakaryocytopoiesis and platelet biology by analyzing expression patterns in 79 subjects with thrombocytosis and controls, and integrated data with transcriptomic and proteomic platforms. We validated a unique 21-miRNA genetic fingerprint associated with thrombocytosis, and demonstrated that a 3-member subset defines essential th ...[more]

PMID: 22869791

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Dataset Information

Thrombocythemic Platelets microRNA Profiling

Publications

Systematic analysis of microRNA fingerprints in thrombocythemic platelets using integrated platforms.

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