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Volume 27
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Exosome-Mediated miRNA Delivery Restores Early Differentiation and Survival Programs in DGCR8-Deficient Mouse Embryonic Stem Cells

by
Tae-Won Ha
1,2,
Hyun Kyu Kim
1,3,
Dongyue No
4,
Jeong Bin Lee
4,
Ahyeon Kim
4,
Bomi Kim
4,
Yena Song
1,
Munkhzul Choijamts
1,
Youngsok Choi
4,
Mihye Lee
1 and
Man Ryul Lee
4,*
1
Soonchunhyang Institute of Medi-bio Science (SIMS), Soon Chun Hyang University, Cheonan 31151, Republic of Korea
2
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel
3
Department of Neurology, School of Medicine, UC Davis, 4625 2nd Ave., Room #3101, Sacramento, CA 95817, USA
4
Department of Stem Cell and Regenerative Biotechnology, KU Institute of Science and Technology, The Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(7), 3000; https://doi.org/10.3390/ijms27073000 (registering DOI)
Submission received: 27 February 2026 / Revised: 9 March 2026 / Accepted: 17 March 2026 / Published: 25 March 2026
(This article belongs to the Special Issue Role of MicroRNAs in Human Diseases: 2nd Edition)
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Abstract

Pluripotent stem cell (PSC) differentiation is orchestrated by intricate autocrine and paracrine signaling networks. Among these, exosomes, key components of the cellular secretome, are implicated as crucial mediators of intercellular communication via delivery of bioactive molecules, including microRNAs (miRNAs). This study investigated the role of exosomal miRNAs in stem cell differentiation using Dgcr8-deficient mouse embryonic stem cells (mESCs), which are incapable of producing mature miRNAs. Although the differentiation capacity was markedly impaired in these cells, partial restoration was observed following treatment with exosomes derived from differentiating wild-type mESCs. Exosomal miRNA uptake was confirmed, and gene ontology analysis revealed significant enrichment of pathways associated with cell fate determination, morphogenesis, and apoptosis regulation. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that exosomal miRNAs modulated multiple osteoinductive signaling cascades, notably the MAPK and TGF-β pathways, in Dgcr8-deficient cells. Apoptotic markers were also downregulated, suggesting a protective effect conferred by the exosomal cargo. Collectively, our results suggest that exosome-mediated delivery of miRNAs may represent a fundamental mechanism by which pluripotent stem cells coordinate stress responses and differentiation trajectories, providing novel insights into the regulation of embryogenesis.
Keywords: mouse embryonic stem cells; DiGeorge syndrome critical region 8 (Dgcr8); exosome; microRNA (miRNA); morphogenetic apoptosis mouse embryonic stem cells; DiGeorge syndrome critical region 8 (Dgcr8); exosome; microRNA (miRNA); morphogenetic apoptosis
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MDPI and ACS Style

Ha, T.-W.; Kim, H.K.; No, D.; Lee, J.B.; Kim, A.; Kim, B.; Song, Y.; Choijamts, M.; Choi, Y.; Lee, M.; et al. Exosome-Mediated miRNA Delivery Restores Early Differentiation and Survival Programs in DGCR8-Deficient Mouse Embryonic Stem Cells. Int. J. Mol. Sci. 2026, 27, 3000. https://doi.org/10.3390/ijms27073000

AMA Style

Ha T-W, Kim HK, No D, Lee JB, Kim A, Kim B, Song Y, Choijamts M, Choi Y, Lee M, et al. Exosome-Mediated miRNA Delivery Restores Early Differentiation and Survival Programs in DGCR8-Deficient Mouse Embryonic Stem Cells. International Journal of Molecular Sciences. 2026; 27(7):3000. https://doi.org/10.3390/ijms27073000

Chicago/Turabian Style

Ha, Tae-Won, Hyun Kyu Kim, Dongyue No, Jeong Bin Lee, Ahyeon Kim, Bomi Kim, Yena Song, Munkhzul Choijamts, Youngsok Choi, Mihye Lee, and et al. 2026. "Exosome-Mediated miRNA Delivery Restores Early Differentiation and Survival Programs in DGCR8-Deficient Mouse Embryonic Stem Cells" International Journal of Molecular Sciences 27, no. 7: 3000. https://doi.org/10.3390/ijms27073000

APA Style

Ha, T.-W., Kim, H. K., No, D., Lee, J. B., Kim, A., Kim, B., Song, Y., Choijamts, M., Choi, Y., Lee, M., & Lee, M. R. (2026). Exosome-Mediated miRNA Delivery Restores Early Differentiation and Survival Programs in DGCR8-Deficient Mouse Embryonic Stem Cells. International Journal of Molecular Sciences, 27(7), 3000. https://doi.org/10.3390/ijms27073000

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