OCT4B expression in PBMNCs suggests the existence of an alternative <i>OCT4</i> promoter

Papamichos, Spyros I.; Lambropoulos, Alexandros; Kotoula, Vassiliki

doi:10.1002/gcc.20707

Cited by 9 publications

(11 citation statements)

References 19 publications

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“…This study also found the regulatory sequences of the human OCT4 promoter in these cells to be densely methylated and hence the OCT4 locus transcriptionally inactive (Papamichos et al 2009). This paradox suggests that transcription of the OCT4A isoform is controlled by the promoter region upstream of exon 1 while OCT4B transcription may be regulated by an alternative promoter possibly located within the OCT4A gene, i.e.…”

Section: Discussionsupporting

confidence: 54%

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

White

Alturaifi²,

Holliman³

et al. 2011

Journal of Endocrinology

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The source of new b-cells in adult human pancreas remains incompletely elucidated with recent studies on rodents providing evidence for neogenesis from progenitor cells in addition to self-replication. The aim of this study was to investigate the expression of pluripotency-associated stem cell markers in proliferative cultures derived from adult human pancreas. Human pancreatic tissue was obtained from deceased donors following ethical approval and relative consent. Isletenriched fraction was separated from the retrieved organ by digestion and density gradient centrifugation. Dissociated cells were seeded in adherent culture forming proliferative 'islet survivor cells' (ISCs). These were characterised at fifth passage by RT-PCR, immunofluorescence staining, FACS, western blot and transfection studies with an OCT4 promoter-driven reporter. Nuclear expression of the pluripotency-associated stem cell marker complex OCT4/SOX2/NANOG was confirmed in ISCs. The phenotype constituted w8% of the overall population. OCT4 biosynthesis was confirmed by western blot and activation of an exogenous OCT4 promoter. Co-expression of pluripotency-associated markers has been confirmed in proliferative primary cells derived from adult human pancreas. Further studies are required to elucidate whether these cells possess functional stem cell characteristics and assess potential for differentiation into pancreatic cell lineages including new b-cells.

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Section: Discussionsupporting

confidence: 54%

“…Recently, expression of OCT4B in peripheral blood mononuclear cells has been reported (Papamichos et al 2009). This study also found the regulatory sequences of the human OCT4 promoter in these cells to be densely methylated and hence the OCT4 locus transcriptionally inactive (Papamichos et al 2009).…”

Section: Discussionmentioning

confidence: 99%

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

White

Alturaifi²,

Holliman³

et al. 2011

Journal of Endocrinology

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“…Contrary to OCT4A, OCT4B cannot sustain the selfrenewal of embryonic cells [22]. In spite of recent focus on OCT4B [26,27], with a current study highlighting its role in stress response [25], the function of OCT4B has not yet been fully established.…”

Section: Discussionmentioning

confidence: 76%

“…OCT4A is principally localized in the nucleus [22,23], and is a fundamental regulator of stemness [24] and maintenance of self-renewal [22]. In contrast OCT4B is predominantly cytoplasmic and its biological function remains to be fully elucidated [25][26][27].…”

Section: Introductionmentioning

confidence: 96%

Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma

Karoubi

Cortes-Dericks

Gugger

et al. 2010

Journal of Surgical Oncology

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“…The classical OCT4 promoter region conserved across species is hypermethylated in peripheral blood mononuclear cells (PBMC) and hypomethylated in human embryonal carcinoma cells, consistent with human OCT4A expression patterns (24). Since OCT4A is not expressed, but OCT4B appears to be expressed, in PBMC (16), Papamichos et al (29) suggest that an alternative promoter may regulate expression of OCT4B in PBMC and other adult somatic cells. In support of this idea, in silico analysis of a 2,000-bp region of the first intron of the OCT4 gene, which is upstream of the first exon of the OCT4B isoform, revealed binding sites for several wellcharacterized transcription factors, including AP1/JUN, NF1, and LEF1 (43).…”

Section: Discussionmentioning

confidence: 75%

Induced overexpression of OCT4A in human embryonic stem cells increases cloning efficiency

Tsai

Chang

Hong

et al. 2014

American Journal of Physiology-Cell Physiology

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Our knowledge of the molecular mechanisms underlying human embryonic stem cell (hESC) selfrenewal and differentiation is incomplete. The level of octamerbinding transcription factor 4 (Oct4), a critical regulator of pluripotency, is precisely controlled in mouse embryonic stem cells. However, studies of human OCT4 are often confounded by the presence of three isoforms and six expressed pseudogenes, which has complicated the interpretation of results. Using an inducible lentiviral overexpression and knockdown system to manipulate OCT4A above or below physiological levels, we specifically examine the functional role of the OCT4A isoform in hESC. (We also designed and generated a comparable series of vectors, which were not functional, for the overexpression and knockdown of OCT4B.) We show that specific knockdown of OCT4A results in hESC differentiation, as indicated by morphology changes, cell surface antigen expression, and upregulation of ectodermal genes. In contrast, inducible overexpression of OCT4A in hESC leads to a transient instability of the hESC phenotype, as indicated by changes in morphology, cell surface antigen expression, and transcriptional profile, that returns to baseline within 5 days. Interestingly, sustained expression of OCT4A past 5 days enhances hESC cloning efficiency, suggesting that higher levels of OCT4A can support self-renewal. Overall, our results indicate that high levels of OCT4A increase hESC cloning efficiency and do not induce differentiation (whereas OCT4B expression cannot be induced in hESC), highlighting the importance of isoform-specific studies in a stable and inducible expression system for human OCT4. Additionally, we demonstrate the utility of an efficient method for conditional gene expression in hESC.human embryonic stem cells; OCT4 isoforms; OCT4A; pluripotency; self-renewal PLURIPOTENT STEM CELLS (PSC) have two unique properties: 1) indefinite self-renewal in culture and 2) the ability to differentiate into tissues from all three embryonic germ layers, or pluripotency (30, 37). Human embryonic stem cells (hESC) and induced pluripotent stem cells, two types of PSC that can be used to model human embryonic development in vitro, represent a promising source of cells for regenerative medicine applications. To realize this potential, a deeper understanding of the genes that regulate self-renewal and differentiation is necessary.Previous studies identified octamer-binding transcription factor 4 (Oct4), sex-determining region Y-box 2 (Sox2), and Nanog as critical transcriptional regulators of early mouse development in vivo and self-renewal and pluripotency of mouse embryonic stem cells (mESC) in vitro (2,6,15,21,22). Oct4, a POU domain transcription factor expressed throughout early mammalian development, is essential for inner cell mass growth and blastocyst survival (22). A 50% increase or decrease in Oct4 expression in mESC promotes differentiation into extraembryonic endoderm and mesoderm, or trophectoderm, respectively, suggesting that the threshold level of Oct...

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OCT4B expression in PBMNCs suggests the existence of an alternative OCT4 promoter

Cited by 9 publications

References 19 publications

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

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

Atypical expression and distribution of embryonic stem cell marker, OCT4, in human lung adenocarcinoma

Induced overexpression of OCT4A in human embryonic stem cells increases cloning efficiency

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