Genome-encoded microRNAs (miRNAs) provide a posttranscriptional regulatory layer that controls the differentiation and function of various cellular systems, including hematopoietic cells. miR-142 is one of the most prevalently expressed miRNAs within the hematopoietic lineage. To address the in vivo functions of miR-142 we utilized a novel reporter and loss-of-function mouse allele that we have recently generated. Here, we show that miR-142 is broadly expressed in the adult hematopoietic system. Our data further reveal that miR-142 is critical for megakaryopoiesis. Thus, genetic miR-142 ablation caused impaired megakaryocyte maturation, inhibition of polyploidization, abnormal proplatelet formation, and thrombocytopenia. Finally, we characterize a network of miR-142-3p targets which collectively controls actin filament homeostasis, thereby ensuring proper execution of actin-dependent proplatelet formation. Our study reveals a pivotal role for miR-142 activity in megakaryocyte maturation and function, and demonstrates a critical contribution of a single miRNA in orchestrating cytoskeletal dynamics and normal haemostasis.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol of the Weizmann Instituter of Science. The protocol, entitled "miR-142 in hematopoietic lineage development" was approved under Permit Numbers: 02930513-3 and 00350111-1. Every effort was made to minimize suffering.
- Elaine Fuchs, Rockefeller University, United States
© 2014, Chapnik et al.
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