Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

Fan, Yubo; Gu, Chaohao; Zhang, Y.L.; Zhong, Bushuai; Wang, L.Z.; Zhou, Zuomin; Wang, Z.Y.; Jia, Ruizhe; Wang, F.

doi:10.4238/2013.december.2.5

Cited by 21 publications

(21 citation statements)

References 29 publications

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“…It has been reported that the overexpression of SIRT1 delays cellular senescence and maintains the adipogenic and osteogenic potential of human BM‐MSCs during prolonged in vitro culture . Overexpression of Sox2 also results in the higher proliferation and differentiation potentials of porcine BM‐MSCs . However, there are no studies that have established whether the modulation of SIRT1 or SOX2 gene has similar effects on the self‐renewal and differentiation potentials of human BM‐MSCs.…”

Section: Resultsmentioning

confidence: 99%

“…SOX2 has been well known to play a crucial role in the maintenance of MSC stemness and its expression decreases during the cellular aging process . Sox2 overexpression enhances the proliferation and differentiation potentials in porcine BM‐MSCs . It has been known that SOX2 regulates the expression of dickkopf‐related protein 1, proto‐oncogene myc (c‐Myc), and yes‐associated protein to maintain MSC stemness and determine their cell fates .…”

Section: Discussionmentioning

confidence: 99%

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SIRT1 Directly Regulates SOX2 to Maintain Self-Renewal and Multipotency in Bone Marrow-Derived Mesenchymal Stem Cells

et al. 2014

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SOX2 is crucial for the maintenance of the self-renewal capacity and multipotency of mesenchymal stem cells (MSCs); however, the mechanism by which SOX2 is regulated remains unclear. Here, we report that RNA interference of sirtuin 1 (SIRT1) in human bone marrow (BM)-derived MSCs leads to a decrease of SOX2 protein, resulting in the deterioration of the self-renewal and differentiation capacities of BM-MSCs. Using immunoprecipitation, we demonstrated direct binding between SIRT1 and SOX2 in HeLa cells overexpressing SOX2. We further discovered that the RNA interference of SIRT1 induces the acetylation, nuclear export, and ubiquitination of SOX2, leading to proteasomal degradation in BM-MSCs. SOX2 suppression by trichostatin A (TSA), a known histone deacetylase inhibitor, was reverted by treatment with resveratrol (0.1 and 1 mM), a known activator of SIRT1 in BM-MSCs. Furthermore, 0.1 and 1 mM resveratrol reduced TSA-mediated acetylation and ubiquitination of SOX2 in BM-MSCs. SIRT1 activation by resveratrol enhanced the colony-forming ability and differentiation potential to osteogenic and adipogenic lineages in a dose-dependent manner. However, the enhancement of self-renewal and multipotency by resveratrol was significantly decreased to basal levels by RNA interference of SOX2. These results strongly suggest that the SIRT1-SOX2 axis plays an important role in maintaining the self-renewal capability and multipotency of BM-MSCs. In conclusion, our findings provide evidence for positive SOX2 regulation by post-translational modification in BMMSCs through the inhibition of nuclear export and subsequent ubiquitination, and demonstrate that SIRT1-mediated deacetylation contributes to maintaining SOX2 protein in the nucleus.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SIRT1 Directly Regulates SOX2 to Maintain Self-Renewal and Multipotency in Bone Marrow-Derived Mesenchymal Stem Cells

et al. 2014

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“…Furthermore, a decrease of proliferation on the lingual side occurred simultaneously with down-regulation of Sox2 expression. Since experimental overexpression of Sox2 in mesenchymal progenitor cells derived from bone marrow resulted in higher proliferation and differentiation [ 32 ], we propose that Sox2 expression on the lingual side is necessary to maintain progenitor cell population proliferation in the successional dental lamina. To support our hypothesis, future work will be necessary to analyse Sox2 expression patterns in other monophyodont species and to design functional experiments.…”

Section: Discussionmentioning

confidence: 99%

Fate of the Molar Dental Lamina in the Monophyodont Mouse

et al. 2015

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The successional dental lamina (SDL) plays an essential role in the development of replacement teeth in diphyodont and polyphyodont animals. A morphologically similar structure, the rudimental successional dental lamina (RSDL), has been described in monophyodont (only one tooth generation) lizards on the lingual side of the developing functional tooth. This rudimentary lamina regresses, which has been proposed to play a role in preventing the formation of future generations of teeth. A similar rudimentary lingual structure has been reported associated with the first molar in the monophyodont mouse, and we show that this structure is common to all murine molars. Intriguingly, a lingual lamina is also observed on the non-replacing molars of other diphyodont mammals (pig and hedgehog), initially appearing very similar to the successional dental lamina on the replacing teeth. We have analyzed the morphological as well as ultrastructural changes that occur during the development and loss of this molar lamina in the mouse, from its initiation at late embryonic stages to its disappearance at postnatal stages. We show that loss appears to be driven by a reduction in cell proliferation, down-regulation of the progenitor marker Sox2, with only a small number of cells undergoing programmed cell death. The lingual lamina was associated with the dental stalk, a short epithelial connection between the tooth germ and the oral epithelium. The dental stalk remained in contact with the oral epithelium throughout tooth development up to eruption when connective tissue and numerous capillaries progressively invaded the dental stalk. The buccal side of the dental stalk underwent keratinisation and became part of the gingival epithelium, while most of the lingual cells underwent programmed cell death and the tissue directly above the erupting tooth was shed into the oral cavity.

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“…Oct4 belongs to the POU family that plays a key role in embryonic development and stem cell pluripotency, it is specifically expressed in pluripotent stem cells [30][31][32][33]. Therefore, in general, Mvh and Oct4 are taken as the markers of germ stem cells.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway

Pan

Sun

et al. 2015

Cell Physiol Biochem

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Background/Aims: Ovarian germline stem cells (OGSCs) have been shown to mainly exist in the ovarian surface epithelium (OSE), but the activity changes of germline stem cells during different reproductive stages and the potential regulatory signaling pathway are still unknown. The Notch signaling pathway plays a key role in cell development, primordial follicles and stem cell proliferation. However, whether it plays a role in the proliferation of OGSCs is unknown. Here, we analyzed the activity changes of germline stem cells and the correlation between germline stem cells and the Notch signaling pathway. Methods: The expression of germline stem cell markers Mvh, Ooc4 and the Notch molecules Notch1, Hes1, and Hes5 were detected during 3 days (3d), and 2, 12, 20 months (2m, 12m, 20m) mouse ovarian surface epithelium samples. DAPT, a specific inhibitor of the Notch pathway, was used to observe the influence of Notch signaling in the germline stem cells. Results: The results showed that the levels of MVH and OCT4 decreased substantially with reproductive age in ovarian surface epithelium, and the same tendency was detected in the Notch signaling molecules Notch1, Hes1 and Hes5. Dual-IF results showed that the germline stem cell markers were co-expressed with Notch molecules in the ovarian surface epithelium. While, the expression of MVH and OCT4 were reduced when the ovaries were treated with DAPT and the levels were attenuated with increasing dose of DAPT. Conclusion: Taken together, our results indicate that the viability of OGSCs decreased with the age of the mouse ovaries, and the activity of OGSCs in the ovarian surface epithelium may be related to the Notch signaling pathway.

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Oct4 and Sox2 overexpression improves the proliferation and differentiation of bone mesenchymal stem cells in Xiaomeishan porcine

Cited by 21 publications

References 29 publications

SIRT1 Directly Regulates SOX2 to Maintain Self-Renewal and Multipotency in Bone Marrow-Derived Mesenchymal Stem Cells

SIRT1 Directly Regulates SOX2 to Maintain Self-Renewal and Multipotency in Bone Marrow-Derived Mesenchymal Stem Cells

Fate of the Molar Dental Lamina in the Monophyodont Mouse

The Expression of Markers Related to Ovarian Germline Stem Cells in the Mouse Ovarian Surface Epithelium and the Correlation with Notch Signaling Pathway

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