MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a
Embryonic stem cells (ESCs) are promising resources for clinical therapies due to their potential to generate multiple cell types. The dynamic expression of de novo methyltransferases (Dnmt3a and Dnmt3b) is essential to ESCs; however, the regulatory mechanism of Dnmt3a or Dnmt3b expression in ESCs i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-03-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506114000087 |
| _version_ | 1828255196241723392 |
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| author | Dandan Yang Guiying Wang Songcheng Zhu Qidong Liu Tingyi Wei Ye Leng Tony Duan Jiuhong Kang |
| author_facet | Dandan Yang Guiying Wang Songcheng Zhu Qidong Liu Tingyi Wei Ye Leng Tony Duan Jiuhong Kang |
| author_sort | Dandan Yang |
| collection | DOAJ |
| description | Embryonic stem cells (ESCs) are promising resources for clinical therapies due to their potential to generate multiple cell types. The dynamic expression of de novo methyltransferases (Dnmt3a and Dnmt3b) is essential to ESCs; however, the regulatory mechanism of Dnmt3a or Dnmt3b expression in ESCs is still poorly understood. Here, we reported that decreased expression of microRNA-495 (miR-495) in the first 2 days of embryoid body (EB) formation was required for mouse embryonic stem cell (mESC) differentiation because repressed mesoderm and endoderm lineages were detected in ectopic miR-495 expression mESCs. This effect was reversed by the function blockade of miR-495. We identified Dnmt3a as a functional target of miR-495 and showed that endogenous miR-495 repressed the expression of Dnmt3a in mESCs. Furthermore, the effect of miR-495 on mESCs could be eliminated by Dnmt3a overexpression. Moreover, miR-495 had no effect on the expression of Dnmt3b despite the findings obtained from previous studies that mainly focused on the common characteristics of the regulatory mechanisms of Dnmt3a and Dnmt3b expression. Thus, our studies not only uncovered a previously uncharacterized function of miR-495 in mESC differentiation but also generated a new idea to explore the mechanisms governing the functional difference between Dnmt3a and Dnmt3b. |
| first_indexed | 2024-04-13T02:11:12Z |
| format | Article |
| id | doaj.art-2fe261a43aa54f96a976e4844288961b |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-04-13T02:11:12Z |
| publishDate | 2014-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-2fe261a43aa54f96a976e4844288961b2022-12-22T03:07:17ZengElsevierStem Cell Research1873-50611876-77532014-03-0112255056110.1016/j.scr.2014.01.005MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3aDandan Yang0Guiying Wang1Songcheng Zhu2Qidong Liu3Tingyi Wei4Ye Leng5Tony Duan6Jiuhong Kang7Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaClinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, PR ChinaEmbryonic stem cells (ESCs) are promising resources for clinical therapies due to their potential to generate multiple cell types. The dynamic expression of de novo methyltransferases (Dnmt3a and Dnmt3b) is essential to ESCs; however, the regulatory mechanism of Dnmt3a or Dnmt3b expression in ESCs is still poorly understood. Here, we reported that decreased expression of microRNA-495 (miR-495) in the first 2 days of embryoid body (EB) formation was required for mouse embryonic stem cell (mESC) differentiation because repressed mesoderm and endoderm lineages were detected in ectopic miR-495 expression mESCs. This effect was reversed by the function blockade of miR-495. We identified Dnmt3a as a functional target of miR-495 and showed that endogenous miR-495 repressed the expression of Dnmt3a in mESCs. Furthermore, the effect of miR-495 on mESCs could be eliminated by Dnmt3a overexpression. Moreover, miR-495 had no effect on the expression of Dnmt3b despite the findings obtained from previous studies that mainly focused on the common characteristics of the regulatory mechanisms of Dnmt3a and Dnmt3b expression. Thus, our studies not only uncovered a previously uncharacterized function of miR-495 in mESC differentiation but also generated a new idea to explore the mechanisms governing the functional difference between Dnmt3a and Dnmt3b.http://www.sciencedirect.com/science/article/pii/S1873506114000087 |
| spellingShingle | Dandan Yang Guiying Wang Songcheng Zhu Qidong Liu Tingyi Wei Ye Leng Tony Duan Jiuhong Kang MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a Stem Cell Research |
| title | MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a |
| title_full | MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a |
| title_fullStr | MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a |
| title_full_unstemmed | MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a |
| title_short | MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a |
| title_sort | mir 495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of dnmt3a |
| url | http://www.sciencedirect.com/science/article/pii/S1873506114000087 |
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