Sox2/Oct4: A delicately balanced partnership in pluripotent stem cells and embryogenesis

Rizzino, Angie; Wuebben, Erin L.

doi:10.1016/j.bbagrm.2016.03.006

Cited by 107 publications

(93 citation statements)

References 78 publications

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“…It is recognized that OCT4 and SOX2 work together closely to regulate a large set of genes that are essential for the self‐renewal and pluripotency of embryonic stem cells (ESCs) . Besides, we considered that β‐catenin may be the potential downstream gene of SOX2.…”

Section: Resultsmentioning

confidence: 99%

“…It is recognized that OCT4 and SOX2 work together closely to regulate a large set of genes that are essential for the selfrenewal and pluripotency of embryonic stem cells (ESCs). (16) Besides, we considered that b-catenin may be the potential downstream gene of SOX2. Therefore, we also tested the effect of OCT4 or b-catenin knockdown on CSCs properties and found that OCT4 or b-catenin knockdown all decreased the sphere formation capacity by a similar magnitude to the effects of SOX2 knockdown in the SK-sphere cells and HOsphere cells ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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SOX2 is required to maintain cancer stem cells in ovarian cancer

et al. 2017

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Ovarian cancer cells can form spheroids under serum‐free suspension culture conditions. The spheroids, which are enriched in cancer stem cells, can result in tumor dissemination and relapse. To identify new targetable molecules in ovarian cancer spheroids, we investigated the differential expression of genes in spheroids compared with that under monolayer culture conditions by qPCR microarray. We identified that SOX2 is overexpressed in spheroids. We then proved that SOX2 expression was increased in successive spheroid generations. Besides, knockdown of SOX2 expression in SKOV3 or HO8910 ovarian cancer spheroid cells decreased spheroid formation, cell proliferation, cell migration, resistance to Cisplatin treatment, tumorigenicity, and the expression of stemness‐related genes and epithelial to mesenchymal transition‐related genes, whereas overexpression of SOX2 in SKOV3 or HO8910 ovarian cancer cells showed the opposite effects. In addition, we found that SOX2 expression was closely associated with chemo‐resistance and poor prognosis in EOC patients. These results strongly suggest that SOX2 is required to maintain cancer stem cells in ovarian cancer. Targeting SOX2 in ovarian cancer may be therapeutically beneficial.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

SOX2 is required to maintain cancer stem cells in ovarian cancer

et al. 2017

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“…It has been reported that a powerful distal enhancer located in the URS of the FGF4 gene can activate FGF4 transcription in F9 cells and ESCs through two cooperative transcription factors, Sox2 and Oct4 [49]. A similar study of mouse Oct4 showed that a distal enhancer could drive Oct4 expression in undifferentiated ESCs, morula, primordial germ cells, and ICM, whereas a proximal enhancer (PE) can block its expression in the epiblast stage [33].…”

Section: Discussionmentioning

confidence: 99%

Construction of a Dual‐Fluorescence Reporter System to Monitor the Dynamic Progression of Pluripotent Cell Differentiation

Sun

Chun

Tae

et al. 2016

Stem Cells International

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Oct4 is a crucial germ line-specific transcription factor expressed in different pluripotent cells and downregulated in the process of differentiation. There are two conserved enhancers, called the distal enhancer (DE) and proximal enhancer (PE), in the 5′ upstream regulatory sequences (URSs) of the mouse Oct4 gene, which were demonstrated to control Oct4 expression independently in embryonic stem cells (ESCs) and epiblast stem cells (EpiSCs). We analyzed the URSs of the pig Oct4 and identified two similar enhancers that were highly consistent with the mouse DE and PE. A dual-fluorescence reporter was later constructed by combining a DE-free-Oct4-promoter-driven EGFP reporter cassette with a PE-free-Oct4-promoter-driven mCherry reporter cassette. Then, it was tested in a mouse ESC-like cell line (F9) and a mouse EpiSC-like cell line (P19) before it is formally used for pig. As a result, a higher red fluorescence was observed in F9 cells, while green fluorescence was primarily detected in P19 cells. This fluorescence expression pattern in the two cell lines was consistent with that in the early naïve pluripotent state and late primed pluripotent state during differentiation of mouse ESCs. Hence, this reporter system will be a convenient tool for screening out ESC-like naïve pluripotent stem cells from other metastable state cells in a heterogenous population.

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“…SOX2 is classified in the SoxB1 family due to the similarity of the amino acid sequence of the high-mobility group box domain (28,29). SOX2 is a transcription factor that serves a primary role in maintaining stem cells in adult tissues, including the CNS.…”

Section: Discussionmentioning

confidence: 99%

Increased NG2 and SOX2 expression is associated with high-grade choroid plexus tumors

Zhao

Feng

et al. 2017

Oncology Letters

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Abstract. The World Health Organization classification of choroid plexus tumors (CPT) includes three distinct grades:Choroid plexus papilloma (CPP), atypical choroid plexus papilloma (ACPP) and choroid plexus carcinoma (CPC). The molecular basis for these pathological distinctions may help to stratify tumors and provide an insight into the clinical behavior of CPTs. In the present study, the progenitor and stem cell markers neuron glia antigen-2 (NG2) and sex-determining region Y-box 2 (SOX2) were investigated as potential biomarkers that may distinguish between distinct CPT grades. Immunohistochemistry was used to determine the expression of NG2 and SOX2 in CPTs (n=34) from Chinese patients (21 males and 13 females) with a mean age of 31.1 years (range, 1-63 years). The proportion of cells stained were scored using a scale between 0 and 3+, where 0 represents no staining and 3+ represents strong staining, and mean scores for each marker were determined on the basis of tumor grade. Pathological diagnosis revealed a distribution of cases as follows: CPP, 25; ACPP, 5; and CPC, 4. NG2 and SOX2 were expressed in CPTs of all grades. The mean labeling indices for CPP, ACPP and CPC were 1.12, 1.80 and 2.75 for NG2, respectively, and 1.20, 2.00 and 3.00 for SOX2, respectively. Statistical analysis of the mean labeling indices revealed a significant association between the expression of NG2 and SOX2 and CPT grade (P= 0.001 and <0.001 for CPP/ACPP and CPP/CPC, respectively). The results of the present study indicated that increased expression of NG2 and SOX2 was associated with higher-grade tumors and that these markers may be useful in determining CPT grade. IntroductionChoroid plexus tumors (CPTs) are rare intracranial neoplasms that derive from the choroid plexus epithelium of the ventricles (1,2). The lesions are commonly located in the lateral and the fourth ventricles, and rarely in the cerebellopontine angle and the third ventricle (3,4). The majority of CPTs arise with clinical symptoms that are associated with hydrocephalus as a result of direct mechanical obstruction of the flow of cerebrospinal fluid (CSF) and arachnoid granulation blockage from hemorrhage and overproduction of CSF (1,5).Treatment of CPTs is currently based on histological diagnosis. According to the World Health Organization (WHO) classification scheme, CPTs are diagnosed as choroid plexus papilloma (CPP, WHO grade I), atypical choroid plexus papilloma (ACPP, WHO grade II) and choroid plexus carcinoma (CPC, WHO grade III) (3). For all classifications, the general treatment strategy is surgical resection unless this is not possible due to tumor location, for example. Gross total resection (GTR) is the indicated course of treatment for CPP as well as for ACPP. CPP is a benign neoplasm and recurrence following GTR is rare, therefore adjuvant radiotherapy and chemotherapy are not generally recommended (2,3,6,7). ACPP cases exhibit atypical histological features along with increased mitotic activity; however, patients with this type of tumor also e...

show abstract

Sox2/Oct4: A delicately balanced partnership in pluripotent stem cells and embryogenesis

Cited by 107 publications

References 78 publications

SOX2 is required to maintain cancer stem cells in ovarian cancer

SOX2 is required to maintain cancer stem cells in ovarian cancer

Construction of a Dual‐Fluorescence Reporter System to Monitor the Dynamic Progression of Pluripotent Cell Differentiation

Increased NG2 and SOX2 expression is associated with high-grade choroid plexus tumors

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