miR-486-5p and miR-22-3p Enable Megakaryocytic Differentiation of Hematopoietic Stem and Progenitor Cells without Thrombopoietin

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, usi...

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Bibliographic Details
Published inInternational journal of molecular sciences Vol. 23; no. 10; p. 5355
Main Authors Kao, Chen-Yuan, Jiang, Jinlin, Thompson, Will, Papoutsakis, Eleftherios T
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 11.05.2022
MDPI
Subjects
1-Phosphatidylinositol 3-kinase
AKT protein
Biological effects
CD34 antigen
Cell differentiation
Cells (biology)
Differentiation
Gene expression
Genotype & phenotype
Hematopoietic stem cells
hematopoietic stem/progenitor cells
Homology
Hypotheses
Kinases
Megakaryocytes
megakaryocytic extracellular vesicle
megakaryopoiesis
microRNA
miRNA
Phenotypes
Progenitor cells
PTEN protein
signaling
SMRT protein
Tensin
Thrombopoietin
TOR protein
hematopoietic stem/progenitor cells
microRNA
megakaryopoiesis
signaling
megakaryocytic extracellular vesicle
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Summary: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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content type line 23
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23105355