Insights into the <i>Nanog</i> gene: A propeller for stemness in primitive stem cells

Zhang, Wei; Sui, Yi; Ni, Jun; Yang, Tao

doi:10.7150/ijbs.16349

Cited by 53 publications

(45 citation statements)

References 70 publications

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“…Higher reductions in cell viability were observed for the CD44 + /CD24subpopulation and spheroids treated with ivermectin compared with paclitaxel. These results were accompanied by the decreased expression of stemness genes nanog, sox-2 and oct-4, previously reported to be highly expressed in CSCs (20).…”

Section: Discussionmentioning

confidence: 60%

Ivermectin as an inhibitor of cancer stem‑like cells

et al. 2017

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The aim of the present study was to demonstrate that ivermectin preferentially inhibited cancer stem‑like cells (CSC) in breast cancer cells and downregulated the expression of 'stemness' genes. Computational searching of DrugBank, a database of approved drugs, was performed using the principles of two‑dimensional similarity searching; the chemical structure of salinomycin was used as a query. Growth inhibition of the breast cancer cell lin e MDA‑MB‑231 by ivermectin was investigated in the total cell population, in cell spheroids and in sorted cells that expressed cluster of differentiation (CD)44+/CD24‑. The effects of ivermectin treatment on the expression of pluripotency and self‑renewal transcription factors, such as homeobox protein nanog (nanog), octamer‑binding protein 4 (oct‑4) and SRY‑box 2 (sox‑2), were evaluated by reverse transcription‑quantitative polymerase chain reaction and western blotting. Ivermectin exhibited a similarity value of 0.78 in reference to salinomycin. Ivermectin demonstrated an inhibitory effect upon the growth of MDA‑MB‑231 cells in the range of 0.2‑8 µM. Ivermectin preferentially inhibits the viability of CSC‑enriched populations (CD44+/CD24‑ and cells growing in spheroids) compared with the total cell population. The opposite pattern was observed with paclitaxel treatment. Ivermectin exposure reduced the expression of nanog, oct‑4 and sox‑2 at the mRNA and protein levels. Ivermectin preferentially inhibited the CSC subpopulation in the MDA‑MB‑231 cells and downregulated the expression of genes involved in the maintenance of pluripotency and self‑renewal.

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Section: Discussionmentioning

confidence: 60%

Ivermectin as an inhibitor of cancer stem‑like cells

et al. 2017

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“…Sox-2 and Oct-4 are known to cooperate to induce multiple subsets of pluripotency genes, including Nanog and themselves, which constitutes complex transcriptional networks [21][22][23]. Nanog also regulates the pluripotency and differentiation of ESCs via its interaction with other transcription factors, such as Oct-4, Sox-2, Klf4, and Slug3/4 [24]. SCF is a ligand of the c-kit tyrosine kinase receptor and plays a crucial role in the proliferation, differentiation, and survival of pluripotent progenitor cells [25].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Fetal Cartilage Progenitor Cells During Long-Term Expansion in a Xeno-Free Medium

Kim

Park

et al. 2018

Tissue Eng Regen Med

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BACKGROUND: Stem cell therapy requires a serum-free and/or chemically-defined medium for commercialization, but it is difficult to find one that supports long-term expansion of cells without compromising their stemness, particularly for novel stem cells. METHODS: In this study, we tested the efficiency of StemPro Ò MSC SFM Xeno Free (SFM-XF), a serum-free medium, for the long-term expansion of human fetal cartilage-derived progenitor cells (hFCPCs) from three donors in comparison to that of the conventional a-Modified Eagle's Medium (a-MEM) supplemented with 10% fetal bovine serum (FBS). RESULTS: We found that SFM-XF supported the expansion of hFCPCs for up to 28-30 passages without significant changes in the doubling time, while a-MEM with 10% FBS showed a rapid increase in doubling time at 10-18 passages depending on the donor. Senescence of hFCPCs was not observed until passage 10 in both media but was induced in approximately 15 and 25% of cells at passage 20 in SFM-XF and a-MEM with 10% FBS, respectively. The colony forming ability of hFCPCs in SFX-XF was also comparable to that in a-MEM with 10% FBS. hFCPCs expressed pluripotency genes like Oct-4, Sox-2, Nanog, SCF, and SSEA4 at passage 20 and 31 in SFM-XF; however, this was not observed when cells were cultured in a-MEM with 10% FBS. The ability of hFCPCs to differentiate into three mesodermal lineages decreased gradually in both media but it was less significant in SFM-XF. Finally we found no chromosomal abnormality after long-term culture of hFCPCs until passage 17 by karyotype analysis. CONCLUSION: These results suggest that SFM-XF supports the long-term expansion of hFCPCs without significant phenotypic and chromosomal changes. This study have also shown that hFCPCs can be mass-produced in vitro, proving their commercial value as a novel source for developing cell therapies. Keywords Human fetal cartilage progenitor cells Á Serum-free medium Á Cell therapy Á Pluripotency Hwal Ran Kim and Jiyoung Kim have contributed equally to this study.

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“…One reason for this could be related to the fact that while we used an antibody to identify the pooled Nanog protein products, there seems to be more than one gene encoding for different Nanog proteins. Although these proteins are structurally similar, and therefore undistinguished by the applied antibody, each one possesses an exclusive function 37 . While the protein product of Nanog1 gene (chromosome 12) is essential for self‐renewal and pluripotency of stem cells, that of NanogP8 (chromosome 15) has a pivotal role in initiating malignant tumors and their progression.…”

Section: Discussionmentioning

confidence: 99%

Expression of stem cell markers in stroma of odontogenic cysts and tumors

Chacham

Almoznino

Zlotogorski‐Hurvitz

et al. 2020

J Oral Pathology Medicine

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Background The stroma of odontogenic cysts/tumors may confer them differential biological behavior. We aimed to investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, and CD34) in the stroma of odontogenic cysts and tumors. CD34 was investigated exclusively as a marker for stromal fibroblast/fibrocyte cells (CD34 + SFCs). CD34 + SFCs were also investigated ultrastructurally. Methods Ten cases each of primary odontogenic keratocyst (OKC), recurrent OKC, dentigerous cyst, ameloblastoma, unicystic ameloblastoma, odontogenic myxoma, and 7 syndromic OKC were included. Results were represented as the mean score (%) of positive cells/field for each marker for each study group. For CD34 + SFCs, results are presented as the mean number of cells/field for each type of lesion. Kruskal‐Wallis and Spearman's correlation statistical tests were used; significance was set at P < .05. Results All markers except Oct4 were expressed by stromal cells in all lesions. Expression of SOX2 was significantly higher in tumors than in cysts (P < .05). CD34 + SFCs were more frequent in cysts than in tumors. Ultrastructurally, CD34 + SFCs were identified for the first time in odontogenic lesions and showed characteristic bipolar/dendritic morphology. Conclusion Among examined stromal stem cell markers, only SOX2 distinguished tumors from cysts. CD34 + SFCs may also contribute to the biological behavior of odontogenic lesions.

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Insights into the Nanog gene: A propeller for stemness in primitive stem cells

Cited by 53 publications

References 70 publications

Ivermectin as an inhibitor of cancer stem‑like cells

Ivermectin as an inhibitor of cancer stem‑like cells

Characterization of Human Fetal Cartilage Progenitor Cells During Long-Term Expansion in a Xeno-Free Medium

Expression of stem cell markers in stroma of odontogenic cysts and tumors

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