miR-486-5p and miR-22-3p Enable Megakaryocytic Differentiation of Hematopoietic Stem and Progenitor Cells without Thrombopoietin |
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| Authors: | Chen-Yuan Kao Jinlin Jiang Will Thompson Eleftherios T. Papoutsakis |
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| Affiliation: | 1.Department of Chemical and Biomolecular Engineering, University of Delaware, 590 Ave. 1743, Newark, DE 19713, USA; (C.-Y.K.); (J.J.); (W.T.);2.Department of Biological Sciences, University of Delaware, 590 Ave. 1743, Newark, DE 19713, USA |
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| Abstract: | Megakaryocytes release submicron size microparticles (MkMPs) in circulation. We have shown that MkMPs target CD34+ hematopoietic stem/progenitor cells (HSPCs) to induce megakaryocytic differentiation, and that small RNAs in MkMPs play an important role in the development of this phenotype. Here, using single-molecule real-time (SMRT) RNA sequencing (RNAseq), we identify the synergetic effect of two microRNAs (miRs), miR-486-5p and miR-22-3p (highly enriched in MkMPs), in driving the Mk differentiation of HSPCs in the absence of thrombopoietin (TPO). Separately, our data suggest that the MkMP-induced Mk differentiation of HSPCs is enabled through JNK and PI3K/Akt/mTOR signaling. The interaction between the two signaling pathways is likely mediated by a direct target of miR-486-5p and a negative regulator of PI3K/Akt signaling, the phosphatase and tensin homologue (PTEN) protein. Our data provide a possible mechanistic explanation of the biological effect of MkMPs in inducing megakaryocytic differentiation of HSPCs, a phenotype of potential physiological significance in stress megakaryopoiesis. |
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| Keywords: | hematopoietic stem/progenitor cells megakaryopoiesis megakaryocytic extracellular vesicle microRNA signaling |
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