Nanog inhibits the switch of myogenic cells towards the osteogenic lineage

Kochupurakkal, Bose; Sarig, Rachel; Fuchs, Ora; Piestun, Dan; Rechavi, Gideon

doi:10.1016/j.bbrc.2007.11.073

Cited by 16 publications

(16 citation statements)

References 23 publications

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“…Alkaline phosphatase activity was performed as previously described. 52 Colony number was determine using Image-Pro Plus analysis software (Media Cybernetics, Rockville, MD, USA). Further characterization and verification of the nature of the reprogrammed clones were performed by QRT-PCR as described below in detail.…”

Section: Methodsmentioning

confidence: 99%

The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele

et al. 2014

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1,5 p53 loss of heterozygosity (p53LOH) is frequently observed in Li-Fraumeni syndrome (LFS) patients who carry a mutant (Mut) p53 germ-line mutation. Here, we focused on elucidating the link between p53LOH and tumor development in stem cells (SCs). Although adult mesenchymal stem cells (MSCs) robustly underwent p53LOH, p53LOH in induced embryonic pluripotent stem cells (iPSCs) was significantly attenuated. Only SCs that underwent p53LOH induced malignant tumors in mice. These results may explain why LFS patients develop normally, yet acquire tumors in adulthood. Surprisingly, an analysis of single-cell sub-clones of iPSCs, MSCs and ex vivo bone marrow (BM) progenitors revealed that p53LOH is a bi-directional process, which may result in either the loss of wild-type (WT) or Mut p53 allele. Interestingly, most BM progenitors underwent Mutp53LOH. Our results suggest that the bi-directional p53LOH process may function as a cell-fate checkpoint. The loss of Mutp53 may be regarded as a DNA repair event leading to genome stability. Indeed, gene expression analysis of the p53LOH process revealed upregulation of a specific chromatin remodeler and a burst of DNA repair genes. However, in the case of loss of WTp53, cells are endowed with uncontrolled growth that promotes cancer.

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Section: Methodsmentioning

confidence: 99%

The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele

et al. 2014

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“…For osteogenesis, MEFs were grown for a few days until subconfluence, then medium was changed to conditioned medium from 293T cells that secrete BMP-4 for the indicated time points. Alkaline Phospatase activity was detected as described [61].…”

Section: Methodsmentioning

confidence: 99%

p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner

et al. 2008

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BackgroundThe tumor suppressor p53 is an important regulator that controls various cellular networks, including cell differentiation. Interestingly, some studies suggest that p53 facilitates cell differentiation, whereas others claim that it suppresses differentiation. Therefore, it is critical to evaluate whether this inconsistency represents an authentic differential p53 activity manifested in the various differentiation programs.Methodology/Principal FindingsTo clarify this important issue, we conducted a comparative study of several mesenchymal differentiation programs. The effects of p53 knockdown or enhanced activity were analyzed in mouse and human mesenchymal cells, representing various stages of several differentiation programs. We found that p53 down-regulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymal cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells.ConclusionsThese comparative studies suggest that, depending on the specific cell type and the specific differentiation program, p53 may exert a positive or a negative effect, and thus can be referred as a “guardian of differentiation” at large.

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“…Therefore, it is unclear whether the putative Nanog protein bands shown on Western blotting (WB), in which frequently only a cropped strip is shown, or the Nanog protein staining shown in immunohistochemistry (IHC) truly represent the Nanog protein. Finally , intriguingly, although the predicated molecular mass of Nanog protein (for both Nanog1 and NanogP8) is ∼35 kD, numerous studies have reported putative Nanog proteins migrating, on SDS-PAGE, at apparent molecular mass of 29 to 80 kD in ES, EC, and somatic cancer cells (Table 1)[2], [5], [17], [24]–[26], [46]–[59]. Even more puzzlingly, the same antibody often seems to detect different ‘Nanog’ protein bands (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Nanog1 in NTERA-2 and Recombinant NanogP8 from Somatic Cancer Cells Adopt Multiple Protein Conformations and Migrate at Multiple M.W Species

et al. 2014

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Human Nanog1 is a 305-amino acid (aa) homeodomain-containing transcription factor critical for the pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells. Somatic cancer cells predominantly express a retrogene homolog of Nanog1 called NanogP8, which is ∼99% similar to Nanog at the aa level. Although the predicted M.W of Nanog1/NanogP8 is ∼35 kD, both have been reported to migrate, on Western blotting (WB), at apparent molecular masses of 29–80 kD. Whether all these reported protein bands represent authentic Nanog proteins is unclear. Furthermore, detailed biochemical studies on Nanog1/NanogpP8 have been lacking. By combining WB using 8 anti-Nanog1 antibodies, immunoprecipitation, mass spectrometry, and studies using recombinant proteins, here we provide direct evidence that the Nanog1 protein in NTERA-2 EC cells exists as multiple M.W species from ∼22 kD to 100 kD with a major 42 kD band detectable on WB. We then demonstrate that recombinant NanogP8 (rNanogP8) proteins made in bacteria using cDNAs from multiple cancer cells also migrate, on denaturing SDS-PAGE, at ∼28 kD to 180 kD. Interestingly, different anti-Nanog1 antibodies exhibit differential reactivity towards rNanogP8 proteins, which can spontaneously form high M.W protein species. Finally, we show that most long-term cultured cancer cell lines seem to express very low levels of or different endogenous NanogP8 protein that cannot be readily detected by immunoprecipitation. Altogether, the current study reveals unique biochemical properties of Nanog1 in EC cells and NanogP8 in somatic cancer cells.

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Nanog inhibits the switch of myogenic cells towards the osteogenic lineage

Cited by 16 publications

References 23 publications

The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele

The onset of p53 loss of heterozygosity is differentially induced in various stem cell types and may involve the loss of either allele

p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner

Nanog1 in NTERA-2 and Recombinant NanogP8 from Somatic Cancer Cells Adopt Multiple Protein Conformations and Migrate at Multiple M.W Species

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