miR-486-5p and miR-22-3p Enable Megakaryocytic Differentiation of Hematopoietic Stem and Progenitor Cells without Thrombopoietin
| Autor: | Chen-Yuan Kao, Jinlin Jiang, Will Thompson, Eleftherios T. Papoutsakis |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Organic Chemistry
PTEN Phosphohydrolase General Medicine Hematopoietic Stem Cells Catalysis Thrombopoiesis Computer Science Applications Inorganic Chemistry MicroRNAs Phosphatidylinositol 3-Kinases Thrombopoietin hematopoietic stem/progenitor cells megakaryopoiesis megakaryocytic extracellular vesicle microRNA signaling Physical and Theoretical Chemistry Proto-Oncogene Proteins c-akt Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 10; Pages: 5355 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23105355 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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