Pluripotency-associated stem cell marker expression in proliferative cell cultures derived from adult human pancreas

White, Margaret A.; Alturaifi, Hussain; Holliman, Graham; Aldibbiat, A; Mahmoud, Aiman; Shaw, James

doi:10.1530/joe-11-0123

Cited by 16 publications

(16 citation statements)

References 34 publications

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“…Moreover, most evidence for the presence of stem/progenitor cell-like populations in nondissociated adult human pancreatic tissue has been limited to detecting equivocal stem cell marker expression in various pancreatic cell types (53,(55)(56)(57). Here for the first time, we report that b-cell stress/hyperglycemia stimulates an adult tissue progenitor cell population within human islets to proliferate and produce more insulin + progeny.…”

Section: Discussionmentioning

confidence: 80%

“…Current regenerative approaches for treating human diabetes has concentrated almost entirely on the production of new b-cells from human pluripotent stem cell systems (52)(53)(54)(55). Moreover, most evidence for the presence of stem/progenitor cell-like populations in nondissociated adult human pancreatic tissue has been limited to detecting equivocal stem cell marker expression in various pancreatic cell types (53,(55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

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Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

et al. 2014

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Endogenous pancreatic multipotent progenitors (PMPs) are ideal candidates for regenerative approaches to compensate for b-cell loss since their b-cell-producing capacities as well as strategic location would eliminate unnecessary invasive manipulations. However, little is known about the status and potentials of PMPs under diabetic conditions. Here we show that b-cell metabolic stress and hyperglycemia enhance the proliferation capacities of adult PMP cells and bias their production of progeny toward b-cells in mouse and human. These effects are dynamic and correlate with functional b-cell regeneration when conditions allow.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

et al. 2014

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“…Interestingly, Oct-4 was found by another group in a low number of cells throughout the adult human pancreas [57]. The cells were very small (1.5–3 µm) and could be described as VSELs, but Oct-4 staining was visible only in cytoplasm [57]. Finally, analysis of methylation of Oct-4 promoter may indicate an active transcription of the gene but is not clear whether it can reveal the specific expression of Oct-4A.…”

Section: Discussionmentioning

confidence: 99%

“…Although Oct-4A is present mostly in nucleus and Oct-4B preferentially localizes to cytoplasm, the localization itself cannot be treated as isoform marker, because Oct-4B can also display nuclear translocation [53], [55]. Interestingly, Oct-4 was found by another group in a low number of cells throughout the adult human pancreas [57]. The cells were very small (1.5–3 µm) and could be described as VSELs, but Oct-4 staining was visible only in cytoplasm [57].…”

Section: Discussionmentioning

confidence: 99%

Murine Bone Marrow Lin−Sca-1+CD45− Very Small Embryonic-Like (VSEL) Cells Are Heterogeneous Population Lacking Oct-4A Expression

et al. 2013

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Murine very small embryonic-like (VSEL) cells, defined by the Lin−Sca-1+CD45− phenotype and small size, were described as pluripotent cells and proposed to be the most primitive hematopoietic precursors in adult bone marrow. Although their isolation and potential application rely entirely on flow cytometry, the immunophenotype of VSELs has not been extensively characterized. Our aim was to analyze the possible heterogeneity of Lin−Sca+CD45− population and investigate the extent to which VSELs characteristics may overlap with that of hematopoietic stem cells (HSCs) or endothelial progenitor cells (EPCs). The study evidenced that murine Lin−Sca-1+CD45− population was heterogeneous in terms of c-Kit and KDR expression. Accordingly, the c-Kit+KDR−, c-Kit−KDR+, and c-Kit−KDR− subpopulations could be distinguished, while c-Kit+KDR+ events were very rare. The c-Kit+KDR− subset contained almost solely small cells, meeting the size criterion of VSELs, in contrast to relatively bigger c-Kit−KDR+ cells. The c-Kit−KDR−FSClow subset was highly enriched in Annexin V-positive, apoptotic cells, hence omitted from further analysis. Importantly, using qRT-PCR, we evidenced lack of Oct-4A and Oct-4B mRNA expression either in whole adult murine bone marrow or in the sorted of Lin−Sca-1+CD45−FSClow population, even by single-cell qRT-PCR. We also found that the Lin−Sca-1+CD45−c-Kit+ subset did not exhibit hematopoietic potential in a single cell-derived colony in vitro assay, although it comprised the Sca-1+c-Kit+Lin− (SKL) CD34−CD45−CD105+ cells, expressing particular HSC markers. Co-culture of Lin−Sca-1+CD45−FSClow with OP9 cells did not induce hematopoietic potential. Further investigation revealed that SKL CD45−CD105+ subset consisted of early apoptotic cells with fragmented chromatin, and could be contaminated with nuclei expelled from erythroblasts. Concluding, murine bone marrow Lin−Sca-1+CD45−FSClow cells are heterogeneous population, which do not express the pluripotency marker Oct-4A. Despite expression of some hematopoietic markers by a Lin−Sca-1+CD45−c-Kit+KDR− subset of VSELs, they do not display hematopoietic potential in a clonogenic assay and are enriched in early apoptotic cells.

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“…Indeed, recent studies have shown SOX2 deregulation in different human cancer types. 18, 19, 20, 21, 22, 23, 24 Several studies present evidence for the presence of SOX2 in stem cell-like progenitor cells in the adult human pancreas , 25, 26 but the function of SOX2 in pancreatic cancer remains unknown.…”

Section: Introductionmentioning

confidence: 99%

SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells

et al. 2013

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SOX2 (Sex-determining region Y (SRY)-Box2) has important functions during embryonic development and is involved in cancer stem cell (CSC) maintenance, in which it impairs cell growth and tumorigenicity. However, the function of SOX2 in pancreatic cancer cells is unclear. The objective of this study was to analyze SOX2 expression in human pancreatic tumors and determine the role of SOX2 in pancreatic cancer cells regulating CSC properties. In this report, we show that SOX2 is not expressed in normal pancreatic acinar or ductal cells. However, ectopic expression of SOX2 is observed in 19.3% of human pancreatic tumors. SOX2 knockdown in pancreatic cancer cells results in cell growth inhibition via cell cycle arrest associated with p21Cip1 and p27Kip1 induction, whereas SOX2 overexpression promotes S-phase entry and cell proliferation associated with cyclin D3 induction. SOX2 expression is associated with increased levels of the pancreatic CSC markers ALDH1, ESA and CD44. Importantly, we show that SOX2 is enriched in the ESA+/CD44+ CSC population from two different patient samples. Moreover, we show that SOX2 directly binds to the Snail, Slug and Twist promoters, leading to a loss of E-Cadherin and ZO-1 expression. Taken together, our findings show that SOX2 is aberrantly expressed in pancreatic cancer and contributes to cell proliferation and stemness/dedifferentiation through the regulation of a set of genes controlling G1/S transition and epithelial-to-mesenchymal transition (EMT) phenotype, suggesting that targeting SOX2-positive cancer cells could be a promising therapeutic strategy.

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Pluripotency-associated stem cell marker expression in proliferative cell cultures derived from adult human pancreas

Cited by 16 publications

References 34 publications

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

Diabetes Enhances the Proliferation of Adult Pancreatic Multipotent Progenitor Cells and Biases Their Differentiation to More β-Cell Production

Murine Bone Marrow Lin−Sca-1+CD45− Very Small Embryonic-Like (VSEL) Cells Are Heterogeneous Population Lacking Oct-4A Expression

SOX2 promotes dedifferentiation and imparts stem cell-like features to pancreatic cancer cells

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