MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a
| Autor: | Jiuhong Kang, Dandan Yang, Ye Leng, Tony Duan, Songcheng Zhu, Guiying Wang, Qidong Liu, Tingyi Wei |
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| Rok vydání: | 2014 |
| Předmět: |
Mesoderm
Cell type Cell Culture Techniques Embryoid body Biology Transfection DNA Methyltransferase 3A Mice medicine Animals DNA (Cytosine-5-)-Methyltransferases lcsh:QH301-705.5 Embryonic Stem Cells Medicine(all) Cell Differentiation Cell Biology General Medicine DNA Methylation Embryonic stem cell Molecular biology Cell biology MicroRNAs medicine.anatomical_structure lcsh:Biology (General) Cell culture embryonic structures DNA methylation Endoderm Developmental Biology |
| Zdroj: | Stem Cell Research, Vol 12, Iss 2, Pp 550-561 (2014) |
| ISSN: | 1873-5061 |
| DOI: | 10.1016/j.scr.2014.01.005 |
| Popis: | 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 2days 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. |
| Databáze: | OpenAIRE |
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