Concise Review: Isoforms of <i>OCT4</i> Contribute to the Confusing Diversity in Stem Cell Biology

Wang, Xia; Dai, Jianwu

doi:10.1002/stem.419

Cited by 188 publications

(206 citation statements)

References 87 publications

(175 reference statements)

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“…It is important that these data are interpreted with caution. From existing literature it is known that primers for POU5F1 can be unreliable [44]. Moreover, the expression of FGF2 could also be associated with MSCs and not only with pluripotency [45].…”

Section: Discussionmentioning

confidence: 99%

Putative mesenchymal stem cells isolated from adult human ovaries

Štimpfel

Cerkovnik

Novaković

et al. 2014

J Assist Reprod Genet

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Purpose The purpose of this study was to show that healthy adult human ovaries can be a source of cells showing typical MSCs characteristics under in vitro conditions. Methods and results The cells, which were isolated from ovarian cortex tissue and named putative ovarian mesenchymal stem cells (PO-MSCs), were compared to bone marrowderived MSCs (BM-MSCs) and to adult human dermal fibroblasts (HDFs). The results of a gene expression analysis using the Human Mesenchymal Stem Cell RT² Profiler™ PCR Array revealed that PO-MSCs were different than fibroblasts. They expressed most of the analyzed genes as BM-MSCs, although some genes were differentially expressed. However, the heterogeneity of PO-MSCs samples was revealed. The PO-MSCs expressed the characteristic genes related to MSCs, such as CD105, CD44, CD90, M-CAM, CD73 and VCAM1. In addition, the expression of markers CD44, CD90, M-CAM and STRO-1 was confirmed in PO-MSCs using immunocytochemistry. The PO-MSCs showed multipotent character, since they were able to differentiate into the cells of adipogenic, osteogenic, neural and pancreatic lineage. Conclusions Healthy adult human ovaries can harbour an interesting population of cells showing typical MSCs characteristics under in vitro conditions and for this reason we named these cells putative MSCs. These cells express genes encoding main MSCs markers and have an interesting differential potential. Based on these results, we propose PO-MSCs as a novel type of MSCs which share some similarities with BMMSCs. Nevertheless they show distinct and specific characteristics and are not fibroblasts.

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Section: Discussionmentioning

confidence: 99%

Putative mesenchymal stem cells isolated from adult human ovaries

Štimpfel

Cerkovnik

Novaković

et al. 2014

J Assist Reprod Genet

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“…Transcription of Oct4 is regulated by a combination of transcription factors and epigenetic mechanisms involving DNA methylation and the remodeling of chromatin structures. [15][16][17] Although the exact metabolic mechanisms contributing to epigenetic regulation in stem cells remain unclear, regulation of amino acid effects on ESC self-renewal and ESC functions via control of epigenetic modulators has been reported. 2,18 In addition, the lack of glucose or Gln is reported to lead to the inhibition of cell cycle progression through gene expression reprogramming in hepatocellular carcinoma, [19][20] suggesting that Gln may interact with an epigenetic modulator.…”

Section: Introductionmentioning

confidence: 99%

Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a

2015

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(2015) Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKCdependent downregulation of HDAC1 and DNMT1/3a, Cell Cycle, 14:20, 3292-3305, DOI: 10.1080/15384101.2015 Although glutamine (Gln) is not an essential amino acid, it is considered a critical substrate in many key metabolic processes that control a variety of physiological functions and are involved in regulating early embryonic development. Thus, we investigated the effect of Gln on regulation of mouse embryonic stem cell (mESC) self-renewal and related signaling pathways. Gln deprivation decreased Oct4 expression as well as expression of cell cycle regulatory proteins. However, Gln treatment retained the expression of cell cycle regulatory proteins and the Oct4 in mESCs, which were blocked by compound 968 (a glutaminase inhibitor). In addition, Gln stimulated PI3K/Akt pathway, which subsequently elicited PKCe translocation to membrane without an influx of intracellular Ca 2+ . Inhibition of Akt and PKC blocked Glninduced Oct4 expression and proliferation. Gln also stimulated mTOR phosphorylation in a time-dependent manner, which abolished by PKC inhibition. Furthermore, Gln increased the cellular population of both Oct4 and bromodeoxyuridine positive cells, suggesting that Gln regulates self-renewal ability of mESCs. Gln induced a decrease in HDAC1, but not in HDAC2, which were blocked by PKC inhibitors. Gln treatment resulted in an increase in global histone acetylation and methylation. In addition, Gln significantly reduced methylation of the Oct4 promoter region through decrease in DNMT1 and DNMT3a expression, which were blocked by PKC and HDAC inhibitors. In conclusion, Gln stimulates mESC proliferation and maintains mESC undifferentiation status through transcription regulation via the Akt, PKCe, and mTOR signaling pathways.

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“…However, compared with the OCT4A, other variants have been less focused even though several years have passed since the identification of the variant in human and mice (Takeda et al 1992, Mizuno & Kosaka 2008. The OCT4 variants have been focused with regard to the following two aspects generally: i) distinct properties compared with OCT4A (Cauffman et al 2006, Lee et al 2006a, Atlasi et al 2008, Guo et al 2012 and ii) an inducer making the improper OCT4A detection (Wang & Dai 2010). However, these studies have also been restricted to human and mice until recently, and even the presence of OCT4 variants is still unclear in pig.…”

Section: Discussionmentioning

confidence: 99%

“…In this study, porcine OCT4 variants were identified first. There is a report addressing that discriminative analysis of OCT4 variants is required because of their similarity in structure (Wang & Dai 2010). As in other species, the presence of porcine OCT4 variants suggests that OCT4 gene is analyzed carefully by distinguishing other variants also in pigs.…”

Section: All Of Oct4 Variants Are Expressed In Developing Embryomentioning

confidence: 99%

“…The OCT4B transcript shares identical exons coding the POU DNA-binding and C-terminal transactivation domains (CTDs) of OCT4A, but the variants have different exon-coding N-terminal transactivation domains (NTDs) (Takeda et al 1992, Mizuno & Kosaka 2008. Moreover, OCT4B1, which is composed of the same exons with OCT4B, contains an additional cryptic exon, which is an intron region in OCT4A and OCT4B transcripts (Atlasi et al 2008, Wang & Dai 2010.…”

Section: Introductionmentioning

confidence: 99%

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Identification and differential expression patterns of porcine OCT4 variants

Hwang

Lee

et al. 2015

Reproduction

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OCT4 encoded by POU5F1 has a crucial role of maintaining pluripotency in embryonic stem cells during early embryonic development and several OCT4 variants have been identified in mouse and human studies. The objective of this study was to identify different variants of OCT4 and analyze their expression patterns in preimplantation porcine embryos and various tissues. In this study, we showed that POU5F1 transcribes its three variants, namely OCT4A, OCT4B, and OCT4B1. The OCT4B transcript consists of exons identical to the major form of the OCT4 variant, OCT4A, with a differential N-terminal domain-coding exon. The structure of OCT4B1 mRNA was the same as that of OCT4B mRNA, but harbored a cryptic exon. Based on these findings, the transcription levels were investigated and found that OCT4B and OCT4B1 made up w20% among the variants in the embryonic stage and this indicates that OCT4A mRNA is dominantly expressed during preimplantation embryo development. In addition, OCT4B mRNA was detected in all tissues examined, while OCT4A and OCT4B1 were detected only in testis but not in other tissues examined. OCT4B1 showed inversely correlated expression with SOX2 and NANOG expression. OCT4A protein was specifically localized to the nuclei, whereas OCT4B was mainly localized to the cytoplasm of the porcine embryos at the blastocyst stage. The findings of this study reveal that the porcine OCT4 gene can potentially encode three variants (OCT4A, OCT4B, and OCT4B1), and they are differentially expressed and would have roles dissimilar between each other in preimplantation embryos and various adult tissues.

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Concise Review: Isoforms of OCT4 Contribute to the Confusing Diversity in Stem Cell Biology

Cited by 188 publications

References 87 publications

Putative mesenchymal stem cells isolated from adult human ovaries

Putative mesenchymal stem cells isolated from adult human ovaries

Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a

Identification and differential expression patterns of porcine OCT4 variants

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