MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a.
MiR-495 suppresses mesendoderm differentiation of mouse embryonic stem cells via the direct targeting of Dnmt3a.
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MiR-495 通过直接靶向 Dnmt3a 抑制小鼠胚胎干细胞的中内胚层分化。
DOI：
10.1016/j.scr.2014.01.005
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发表时间：
2014-03
影响因子：
1.2
通讯作者：
Jiuhong Kang
中科院分区：
文献类型：
--
作者：
Tingyi Wei;Ye Leng;Tony Duan;Jiuhong Kang
胚胎干细胞（ESCs）是临床治疗的有前途的资源，因为它们具有产生多种细胞类型的潜力。新生甲基转移酶（Dnmt 3a和Dnmt 3b）的动态表达对ESC至关重要;然而，Dnmt 3a或Dnmt 3b在ESC中表达的调控机制仍然知之甚少。在这里，我们报道了在胚状体（EB）形成的前2天中microRNA-495（miR-495）的表达降低是小鼠胚胎干细胞（mESC）分化所需的，因为在异位miR-495表达mESC中检测到受抑制的中胚层和内胚层谱系。这种作用被miR-495的功能阻断逆转。我们将Dnmt 3a鉴定为miR-495的功能靶点，并表明内源性miR-495抑制了mESC中Dnmt 3a的表达。此外，miR-495对mESCs的影响可以通过Dnmt 3a过表达来消除。此外，miR-495对Dnmt 3b的表达没有影响，尽管从先前的研究中获得的结果主要集中在Dnmt 3a和Dnmt 3b表达调控机制的共同特征上。因此，我们的研究不仅揭示了miR-495在mESC分化中以前未表征的功能，而且为探索Dnmt 3a和Dnmt 3b之间功能差异的机制提供了新的思路。
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.
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影响因子：
64.5
作者：
Thomson M;Liu SJ;Zou LN;Smith Z;Meissner A;Ramanathan S
通讯作者：
Ramanathan S
影响因子：
23.9
作者：
Smith KN;Singh AM;Dalton S
通讯作者：
Dalton S
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
64.5
作者：
Okano, M;Bell, DW;Li, E
通讯作者：
Li, E
DOI：
10.1016/s0093-3619(08)70915-8
发表时间：
2008
期刊：
Yearbook of Dermatology and Dermatologic Surgery
影响因子：
--
作者：
B. Thiers
通讯作者：
B. Thiers