NPR-A regulates self-renewal and pluripotency of embryonic stem cells.
NPR-A regulates self-renewal and pluripotency of embryonic stem cells.
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DOI：
10.1038/cddis.2011.10
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发表时间：
2011-03-10
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
胚胎干细胞的自我更新和多能性是由多个信号级联反应和内在因子（如Oct4、Nanog和Sox2）的表达维持的。在胚胎干细胞中调节这些信号级联反应的机制引起了极大的兴趣。最近，我们已经证明钠肽受体A （NPR-A）是心房和脑钠肽（分别为ANP和BNP）的特异性受体，在植入前胚胎和胚胎干细胞中表达。在这里，我们研究了NPR-A是否参与ES细胞多能性的维持。RNA干扰介导的下调NPR-A导致表型改变，表明分化，下调多能因子（如Oct4， Nanog和Sox2）和上调分化基因。NPR-A敲低也导致磷酸化Akt的显著下调。此外，在细胞周期的G1期，NPR-A敲低诱导ES细胞聚集。有趣的是，我们发现ANP在自我更新的ES细胞中表达，而其水平在ES细胞分化后降低。用ANP处理ES细胞可上调Oct4、Nanog和磷酸化Akt的表达，这种上调依赖于NPR-A信号，因为用NPR-A拮抗剂或cgmp依赖性蛋白激酶抑制剂预处理后，这种上调完全逆转。这些发现为NPR-A在维持胚胎干细胞的自我更新和多能性方面提供了新的作用。
Self-renewal and pluripotency of embryonic stem (ES) cells are maintained by several signaling cascades and by expression of intrinsic factors, such as Oct4, Nanog and Sox2. The mechanism regulating these signaling cascades in ES cells is of great interest. Recently, we have demonstrated that natriuretic peptide receptor A (NPR-A), a specific receptor for atrial and brain natriuretic peptides (ANP and BNP, respectively), is expressed in pre-implantation embryos and in ES cells. Here, we examined whether NPR-A is involved in the maintenance of ES cell pluripotency. RNA interference-mediated knockdown of NPR-A resulted in phenotypic changes, indicative of differentiation, downregulation of pluripotency factors (such as Oct4, Nanog and Sox2) and upregulation of differentiation genes. NPR-A knockdown also resulted in a marked downregulation of phosphorylated Akt. Furthermore, NPR-A knockdown induced accumulation of ES cells in the G1 phase of the cell cycle. Interestingly, we found that ANP was expressed in self-renewing ES cells, whereas its level was reduced after ES cell differentiation. Treatment of ES cells with ANP upregulated the expression of Oct4, Nanog and phosphorylated Akt, and this upregulation depended on NPR-A signaling, because it was completely reversed by pretreatment with either an NPR-A antagonist or a cGMP-dependent protein kinase inhibitor. These findings provide a novel role for NPR-A in the maintenance of self-renewal and pluripotency of ES cells.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
DOI：
10.1042/bj20091439
发表时间：
2010-02-09
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Go Y;Kang I;Han YM;Kim J
通讯作者：
Kim J
DOI：
10.1073/pnas.94.26.14730
发表时间：
1997-12-23
影响因子：
11.1
作者：
Oliver, PM;Fox, JE;Maeda, N
通讯作者：
Maeda, N
影响因子：
64.5
作者：
Niwa, H;Toyooka, T;Rossant, J
通讯作者：
Rossant, J
影响因子：
15.9
作者：
MORISHITA, R;GIBBONS, GH;DZAU, VJ
通讯作者：
DZAU, VJ