Transfer of MicroRNAs by Embryonic Stem Cell Microvesicles
Open accessAbstract
Microvesicles are plasma membrane-derived vesicles released into the extracellular environment by a variety of cell types. Originally characterized from platelets, microvesicles are a normal constituent of human plasma, where they play an important role in maintaining hematostasis. Microvesicles have been shown to transfer proteins and RNA from cell to cell and they are also believed to play a role in intercellular communication. We characterized the RNA and protein content of embryonic stem cell microvesicles and show that they can be engineered to carry exogenously expressed mRNA and protein such as green fluorescent protein (GFP). We demonstrate that these engineered microvesicles dock and fuse with other embryonic stem cells, transferring their GFP. Additionally, we show that embryonic stem cells microvesicles contain abundant microRNA and that they can transfer a subset of microRNAs to mouse embryonic fibroblasts in vitro. Since microRNAs are short (21-24 nt), naturally occurring RNAs that regulate protein translation, our findings open up the intriguing possibility that stem cells can alter the expression of genes in neighboring cells by transferring microRNAs contained in microvesicles. Embryonic stem cell microvesicles may be useful therapeutic tools for transferring mRNA, microRNAs, protein, and siRNA to cells and may be important mediators of signaling within stem cell niches.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
microRNA's presence in exosomes has been reported in different cells and cancer types.
“microRNA's presence in exosomes have been already reported in different cells and cancer types (44–50).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [49]
The Results section reports miRNAs in embryonic stem-cell microvesicles, and the Introduction reports prior findings in peripheral-blood and ovarian-tumor microvesicles. The paper does not identify these vesicles as exosomes or establish miRNA presence across multiple cancer types. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14
Lee, R. C., Feinbaum, R. L., & Ambros, V. (1993) · Cell · doi:10.1016/0092-8674(93)90529-y · Cited by 12,948 · see citing works
Wightman, B., Ha, I., & Ruvkun, G. (1993) · Cell · doi:10.1016/0092-8674(93)90530-4 · Cited by 4,292 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- [1]Wolf P 1967 The nature and significance of platelet products in human plasma. Br J Haematol 13 269 288 6025241
- [2]Abrahams VM Straszewski SL Kamsteeg M Hanczaruk B Schwartz PE 2003 Epithelial ovarian cancer cells secrete functional Fas ligand. Cancer Res 63 5573 5581 14500397
- [3]Mack M Kleinschmidt A Bruhl H Klier C Nelson PJ 2000 Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nat Med 6 769 775 10888925
- [4]Martinez MC Tesse A Zobairi F Andriantsitohaina R 2005 Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 288 H1004 1009 15706036
- [5]Morel O Toti F Hugel B Freyssinet JM 2004 Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 11 156 164 15257014
- [6]Ratajczak J Miekus K Kucia M Zhang J Reca R 2006 Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20 847 856 16453000
- [7]Ratajczak J Wysoczynski M Hayek F Janowska-Wieczorek A Ratajczak MZ 2006 Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20 1487 1495 16791265
- [8]Sloand EM Maciejewski JP Dunn D Moss J Brewer B 1998 Correction of the PNH defect by GPI-anchored protein transfer. Blood 92 4439 4445 9834251
- [9]Greco V Hannus M Eaton S 2001 Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106 633 645 11551510
- [10]Baj-Krzyworzeka M Szatanek R Weglarczyk K Baran J Urbanowicz B 2006 Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 55 808 818 16283305 PMC11030663
- [11]Beaudoin AR Grondin G 1991 Shedding of vesicular material from the cell surface of eukaryotic cells: different cellular phenomena. Biochim Biophys Acta 1071 203 219 1958687
- [12]Greenwalt TJ 2006 The how and why of exocytic vesicles. Transfusion 46 143 152 16398744
- [13]Hugel B Martinez MC Kunzelmann C Freyssinet JM 2005 Membrane microparticles: two sides of the coin. Physiology (Bethesda) 20 22 27 15653836
- [14]Sims PJ Wiedmer T Esmon CT Weiss HJ Shattil SJ 1989 Assembly of the platelet prothrombinase complex is linked to vesiculation of the platelet plasma membrane. Studies in Scott syndrome: an isolated defect in platelet procoagulant activity. J Biol Chem 264 17049 17057 2793843
- [15]Boulanger CM Amabile N Tedgui A 2006 Circulating microparticles: a potential prognostic marker for atherosclerotic vascular disease. Hypertension 48 180 186 16801490
- [16]Lagos-Quintana M Rauhut R Lendeckel W Tuschl T 2001 Identification of novel genes coding for small expressed RNAs. Science 294 853 858 11679670
- [17]Lau NC Lim LP Weinstein EG Bartel DP 2001 An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294 858 862 11679671
- [18]Lee RC Ambros V 2001 An extensive class of small RNAs in Caenorhabditis elegans. Science 294 862 864 11679672
- [19]Hunter MP Ismail N Zhang X Aguda BD Lee EJ 2008 Detection of microRNA expression in human peripheral blood microvesicles. PLoS ONE 3 e3694 19002258 PMC2577891
- [20]Dahiya N Sherman-Baust CA Want TL Davidson B Shih IeM 2008 MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS ONE 3 e2436 18560586 PMC2410296
- [21]Yang Z Stratton C Francis PJ Kleinman ME Tan PL 2008 Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N Engl J Med 359 1456 1463 18753640 PMC2573951
- [22]Chen C Ridzon DA Broomer AJ Zhou Z Lee DH 2005 Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 33 e179 16314309 PMC1292995
- [23]Houbaviy HB Murray MF Sharp PA 2003 Embryonic stem cell-specific MicroRNAs. Dev Cell 5 351 358 12919684
- [24]Suh MR Lee Y Kim JY Kim SK Moon SH 2004 Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270 488 498 15183728
- [25]Del Conde I Shrimpton CN Thiagarajan P Lopez JA 2005 Tissue-factor-bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation. Blood 106 1604 1611 15741221
- [26]Fritzsching B Schwer B Kartenbeck J Pedal A Horejsi V 2002 Release and intercellular transfer of cell surface CD81 via microparticles. J Immunol 169 5531 5537 12421929
- [27]Martinez MC Larbret F Zobairi F Coulombe J Debili N 2006 Transfer of differentiation signal by membrane microvesicles harboring hedgehog morphogens. Blood 108 3012 3020 16778137
- [28]Tahinci E Lee E 2004 The interface between cell and developmental biology. Curr Opin Genet Dev 14 361 366 15261651
- [30]Moss EG Tang L 2003 Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. Dev Biol 258 432 442 12798299
- [32]Abrahante JE Daul AL Li M Volk ML Tennessen JM 2003 The Caenorhabditis elegans hunchback-like gene lin-57/hbl-1 controls developmental time and is regulated by microRNAs. Dev Cell 4 625 637 12737799
- [33]Lin SY Johnson SM Abraham M Vella MC Pasquinelli A 2003 The C elegans hunchback homolog, hbl-1, controls temporal patterning and is a probable microRNA target. Dev Cell 4 639 650 12737800
- [34]Quesenberry PJ Aliotta JM 2008 The paradoxical dynamism of marrow stem cells: considerations of stem cells, niches, and microvesicles. Stem Cell Rev 4 137 147 18665337 PMC4495665
Cited by
Sorted by citations
Adipose-derived circulating miRNAs regulate gene expression in other tissues
Thomou, T., Mori, M. A., Dreyfuss, J. M., Konishi, M., Sakaguchi, M., Wolfrum, C., Rao, T. N., Winnay, J. N., Garcia-Martin, R., Grinspoon, S. K., et al. (2017) · Nature · doi:10.1038/nature21365 · Cited by 1,539 · see citing works
Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis
Zhou, W., Fong, M. Y., Min, Y., Somlo, G., Liu, L., Palomares, M. R., Yu, Y., Chow, A., O’Connor, S. T. F., Chin, A. R., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.007 · Cited by 1,476 · see citing works
The role of microRNAs in human diseases
Tüfekci, K. U., Öner, M. G., Meuwissen, R. L. J., & Genç, Ş. (2014) · Methods in molecular biology · doi:10.1007/978-1-62703-748-8_3 · Cited by 566 · see citing works
Turturici, G., Tinnirello, R., Sconzo, G., & Geraci, F. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00228.2013 · Cited by 483 · see citing works
Genetically Engineered Microvesicles Carrying Suicide mRNA/Protein Inhibit Schwannoma Tumor Growth
Mizrak, A., Bolukbasi, M. F., Ozdener, G. B., Brenner, G. J., Madlener, S., Erkan, E. P., Ströbel, T., Breakefield, X. O., & Saydam, O. (2013) · Molecular Therapy · doi:10.1038/mt.2012.161 · Cited by 337 · see citing works
Xu, J.-F., Yang, G.-H., Pan, X.-H., Zhang, S.-J., Zhao, C., Qiu, B.-S., Gu, H.-F., Hong, J.-F., Cao, L., Chen, Y., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0114627 · Cited by 235 · see citing works
Povero, D., Panera, N., Eguchi, A., Johnson, C. D., Papouchado, B. G., de Araujo Horcel, L., Pinatel, E. M., Alisi, A., Nobili, V., & Feldstein, A. E. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.07.007 · Cited by 221 · see citing works
Monfared, H., Jahangard, Y., Nikkhah, M., Mirnajafi-Zadeh, J., & Mowla, S. J. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00782 · Cited by 123 · see citing works
Guescini, M., Maggio, S., Ceccaroli, P., Battistelli, M., Annibalini, G., Piccoli, G., Sestili, P., & Stocchi, V. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18112488 · Cited by 59 · see citing works
- Authors
- Yuan, A., Farber, E. L., Rapoport, A. L., Tejada, D., Deniskin, R., Akhmedov, N. B., & Farber, D. B.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Farber, Debora B.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-03-06
- Volume
- 4
- Issue
- 3
- Pages
- e4722
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2648987
- OpenAlex
- W2014455148
- Cited by
- 416
- References
- 3
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 13 · 2019: 24 · 2018: 25 · 2017: 23 · 2016: 41 · 2015: 46 · 2014: 39 · 2013: 37 · 2012: 52
- FWCI
- 16.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Vision of Children Foundation
- Hope For Vision
- National Institutes of Health
- National Eye Institute (R21EY018739, EY018739)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- microvesicles, embryonic stem cells, microRNA transfer, extracellular vesicles, intercellular communication, microRNA delivery, mouse embryonic fibroblasts, cell fusion
- MeSH terms
- Animals, Biological Transport, Cell Communication, MicroRNAs, Green Fluorescent Proteins, Mice, Embryonic Stem Cells, Cell-Derived Microparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review