Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway

Liao, Feng-Ling; Tan, Lin; Liu, Hua; Wang, Jinju; Ma, Xiaotang; Zhao, Bin; Chen, Yanfang; Bihl, Ji C.; Yang, Yi; Chen, Ri-ling

doi:10.1038/aps.2017.130

Cited by 34 publications

(23 citation statements)

References 38 publications

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“…Mesenchymal stem cell-derived exosomes show a potential effect on the alteration of microRNA profiles and induce osteogenic differentiation, depending on the stage of differentiation, through modulation of the Wnt signalling pathway and endocytosis [254]. Hematopoietic stem cell-derived exosomes promote the hematopoietic diiferentiation of mouse embryonic stem cells through inhibiting the mir126/Notch pathway [255]. Exosomes derived from bladder cancer cells are internalized by fibroblasts and promote the proliferation and expression of CAF markers.…”

Section: Biological Functions Of Exosomesmentioning

confidence: 99%

Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Gurunathan

Kang

Jeyaraj

et al. 2019

Cells

856

739

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Exosomes are extracellular vesicles that contain a specific composition of proteins, lipids, RNA, and DNA. They are derived from endocytic membranes and can transfer signals to recipient cells, thus mediating a novel mechanism of cell-to-cell communication. They are also thought to be involved in cellular waste disposal. Exosomes play significant roles in various biological functions, including the transfer of biomolecules such as RNA, proteins, enzymes, and lipids and the regulation of numerous physiological and pathological processes in various diseases. Because of these properties, they are considered to be promising biomarkers for the diagnosis and prognosis of various diseases and may contribute to the development of minimally invasive diagnostics and next generation therapies. The biocompatible nature of exosomes could enhance the stability and efficacy of imaging probes and therapeutics. Due to their potential use in clinical applications, exosomes have attracted much research attention on their roles in health and disease. To explore the use of exosomes in the biomedical arena, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are well-understood. Herein, we discuss the history, biogenesis, release, isolation, characterization, and biological functions of exosomes, as well as the factors influencing their biogenesis and their technical and biological challenges. We conclude this review with a discussion on the future perspectives of exosomes.

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Section: Biological Functions Of Exosomesmentioning

confidence: 99%

Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Gurunathan

Kang

Jeyaraj

et al. 2019

Cells

856

739

View full text Add to dashboard Cite

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“…Based on published literature, miR concentrations from 1 nM to 3.6 µM have been used to transfect HSPCs. [33][34][35] In the following studies, since the seven MkMP miRs we examined are highly abundant in MkMPs, and due to the fact that multiple MkMPs are taken up by a single recipient CD34 + HSPC, 16 we hypothesized that higher concentrations of these seven miRs are likely delivered to CD34 + HSPC via MkMPs. Therefore, we chose 8 µM of miR mimics for the following experiments.…”

Section: Mir-486-5p In Combination With Mir-22-3p Largely Recapitulatmentioning

confidence: 99%

Combinatorial effect of miR-486-5p & miR-22-3p mimics thrombopoietin’s impact on hematopoietic stem & progenitor cells

Kao

Jiang

Papoutsakis

2020

Preprint

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Word Count (Text): 5429 Word Count (Abstract): 246 Figure Count: 7Table Count: 2 Reference Count: 61 Key Points• miR-486-5p and miR-22-3p drive megakaryocytic differentiation in the absence of thrombopoietin.• Megakaryocytic microparticles trigger megakaryocytic differentiation of CD34 + cells through JNK and PI3K/Akt/mTOR signaling. AbstractMegakaryocytes shed and release submicron size microparticles (MkMPs), the most abundant microparticle in circulation. We have previously reported that MkMPs target peripheral-blood CD34 + hematopoietic stem/progenitor cells (HSPCs) to induce megakaryocytic differentiation and proliferation, and that small RNAs delivered to HSPCs via MkMPs play an important role in the development of this phenotype. Here, using single-molecule real-time (SMRT) RNA sequencing (RNAseq), we identify the top seven most abundant microRNAs (miRs) in MkMPs as potential candidates in mediating the effect of MkMPs on HSPCs. Using miR mimics, we demonstrate that among the seven most abundant miRs, two, miR-486-5p and miR-22-3p, are able to drive the Mk differentiation of HSPCs in the absence of thrombopoietin (TPO). The effect of these two miRs is comparable to the TPO-or MkMP-induced megakaryocytic differentiation of HSPCs, thus suggesting that these two miRs are responsible for this MkMPinduced phenotype. To probe the signaling through which MkMPs might enable this phenotype, we used kinase inhibitors of potential signaling pathways engaged in megakaryocytic differentiation. Our data suggest that MkMP-induced Mk differentiation of HSPCs is enabled through JNK and PI3K/Akt/mTOR signaling. Our data show that MkMPs activate Akt and mTOR phosphorylation. Furthermore, MkMPs downregulate PTEN expression, a direct target of miR-486-5p and a negative regulator of PI3K/Akt signaling, via JNK signaling. Taken together, our data provide a mechanistic understanding of the biological effect of MkMPs in inducing megakaryocytic differentiation of HSPCs, which, as was previously suggested, is a phenotype of potential physiological significance in stress megakaryopoiesis.

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“…Exosomes were considered to be a mechanism for discarding cell garbage until a number of studies suggested that they were nano-sized vesicles that serve as mediators for intercellular communication through the delivery of proteins, lipids, nucleic acids, or other components in or within their lipid bilayer membrane to neighboring or distant cells. Although accumulating studies have indicated the crucial role of exosomes in various physi-ological and pathological processes, including tumor metastasis, neurodegeneration, and tissue repair [4][5][6][7][8] , the regulation of biogenesis and cargo loading is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools

et al. 2018

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Exosomes are nano-sized vesicles that serve as mediators for intercellular communication through the delivery of cargo, including protein, lipids, nucleic acids or other cellular components, to neighboring or distant cells. Exosomal cargo may vary in response to different physiological or pathological conditions. The endosomal sorting complex required for transport (ESCRT) family has been widely accepted as a key mechanism in biogenesis and cargo sorting. On the other hand, accumulating evidence show that ESCRT-independent pathways exist. Due to the critical role of exosomes in intercellular communications in delivering cargo to recipient cells, exosomes have been investigated as a vector for the delivery of endogenous or exogenous cargo for therapeutic purposes. But the number of exosomes produced by cells is limited, which hampers their application. Synthetic exosome-mimics have been fabricated and investigated as a therapeutic tool for drug delivery. This review focuses on ESCRT-independent regulation of cargo loading into exosomes, including lipid raft and ceramide-mediated mechanisms, and reported exosomes or exosome-mimics with therapeutic effects.

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Hematopoietic stem cell-derived exosomes promote hematopoietic differentiation of mouse embryonic stem cells in vitro via inhibiting the miR126/Notch1 pathway

Cited by 34 publications

References 38 publications

Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Review of the Isolation, Characterization, Biological Function, and Multifarious Therapeutic Approaches of Exosomes

Combinatorial effect of miR-486-5p & miR-22-3p mimics thrombopoietin’s impact on hematopoietic stem & progenitor cells

Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools

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