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Mitofusin 2 (MFN2) is a regulatory protein participating in mitochondria dynamics, cell proliferation, death, differentiation, and so on. This study aims at revealing the functional role of MFN2 in the pluripotency maintenance and primitive differetiation of embryonic stem cell (ESCs). A dox inducible silencing and routine overexpressing approach was used to downregulate and upregulate MFN2 expression, respectively. We have compared the morphology, cell proliferation, and expression level of pluripotent genes in various groups. We also used directed differentiation methods to test the differentiation capacity of various groups. The Akt signaling pathway was explored by the western blot assay. MFN2 upregulation in ESCs exhibited a typical cell morphology and similar cell proliferation, but decreased pluripotent gene markers. In addition, MFN2 overexpression inhibited ESCs differentiation into the mesendoderm, while MFN2 silencing ESCs exhibited a normal cell morphology, slower cell proliferation and elevated pluripotency markers. For differentiation, MFN2 silencing ESCs exhibited enhanced three germs' differentiation ability. Moreover, the protein levels of phosphorylated Akt308 and Akt473 decreased in MFN2 silenced ESCs, and recovered in the neural differentiation process. When treated with the Akt inhibitor, the neural differentiation capacity of the MFN2 silenced ESCs can reverse to a normal level. Taken together, the data indicated that the appropriate level of MFN2 expression is essential for pluripotency and differentiation capacity in ESCs. The increased neural differentiation ability by MFN2 silencing is strongly related to the Akt signaling pathway.
This article was published in the following journal.
Name: Journal of cellular physiology
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The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.
A homeodomain protein and transcription regulator that functions in BLASTOCYST INNER CELL MASS and EMBRYONIC STEM CELL proliferation and CELL SELF RENEWAL. It confers pluripotency on embryonic stem cells and prevents their differentiation towards extraembryonic ENDODERM and trophectoderm (TROPHOBLAST) CELL LINEAGES.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Cells from adult organisms that have been reprogrammed into a pluripotential state similar to that of EMBRYONIC STEM CELLS.
Cell-surface molecules that exhibit lineage-restricted patterns of expression during EMBRYONIC DEVELOPMENT. The antigens are useful markers in the identification of EMBRYONIC STEM CELLS.
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