Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages

Onyango, Patrick; Jiang, Shan; Uejima, Hiroshi; Shamblott, Michael J.; Gearhart, John D.; Cui, Hengmi; Feinberg, Andrew P.

doi:10.1073/pnas.152327599

Cited by 61 publications

(39 citation statements)

References 24 publications

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“…The cellular heterogeneity of the starting population is a complicating factor-fetal gonads contain cell types other than PGCs. Pluripotent cells can spontaneously differentiate in culture [7], and the difficulty in managing the differentiation status of hEG cells has been recognized by others [45]. Furthermore, a varying degree of cell death occurs within EBs, as observed for ES cells [7].…”

Section: Discussionmentioning

confidence: 98%

Derivation of Human Embryonic Germ Cells: An Alternative Source of Pluripotent Stem Cells

et al. 2003

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Based on evidence suggesting similarities to human embryonic stem cells, human embryonic germ (hEG) cells have been advocated as an alternative pluripotent stem cell resource but have so far received limited attention. To redress this imbalance, human fetal gonads were collected for the isolation and culture of primordial germ cells at 7-9 weeks postconception. We provide evidence for the derivation, culture, and differentiation of hEG cells in vitro. This evidence includes the expression of markers characteristic of pluripotent cells, the retention of normal XX or XY karyotypes, and the demonstration of pluripotency, as suggested by the expression of markers indicative of differentiation along the three germ lineages (ectoderm, mesoderm, and endoderm) and an associated loss of pluripotent markers. In assessing this differentiation, however, we also demonstrate a hitherto unacknowledged overlap in gene expression profiles between undifferentiated and differentiated cell types, highlighting the difficulty in ascribing cell lineage by gene expression analyses. Furthermore, we draw attention to the problems inherent in the management of these cells in prolonged culture, chiefly the difficulty in preventing spontaneous differentiation, which hinders the isolation of pure, undifferentiated clonal lines. While these data advocate the pursuit of pluripotent hEG cell studies with relevance to early human embryonic development, culture limitations carry implications for their potential applicability to ambitious cell replacement therapies.

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Section: Discussionmentioning

confidence: 98%

Derivation of Human Embryonic Germ Cells: An Alternative Source of Pluripotent Stem Cells

et al. 2003

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“…The IGF-2 gene, which is located in the vicinity of the human INS gene, is imprinted and paternally expressed [26]. However, it is uncertain whether the human INS-VNTR region is imprinted.…”

Section: Discussionmentioning

confidence: 99%

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

et al. 2004

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Aims/hypothesis. The class III allele of the variablenumber-of-tandem-repeats polymorphism located 5′ of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced insulin response among NGT individuals. Methods. We investigated the impact of the class III allele on Type 2 diabetes susceptibility in a case-control study involving 1462 Type 2 diabetic patients and 4931 NGT subjects. We also examined the potential impact of the class III allele in genotype-quantitative trait studies in three Danish study populations containing (i) 358 young healthy subjects; (ii) 4444 middleaged NGT subjects, 490 subjects with IFG and 678 subjects with IGT; and (iii) 221 NGT subjects, of whom one parent had Type 2 diabetes.Results. There was no difference in frequency of the class III allele or in genotype distribution between the 1462 Type 2 diabetic patients and the 4931 NGT subjects. Among the 358 young subjects the class III/III carriers had significantly reduced post-IVGTT acute serum insulin and C-peptide responses (p=0.04 and 0.03 respectively). However, among the 4444 middleaged subjects we failed to demonstrate any association between the class III allele and post-OGTT serum insulin and C-peptide levels. Conclusions/interpretation. The class III allele of the INS-VNTR does not confer susceptibility to Type 2 diabetes or consistent alterations in glucose-induced insulin release in the examined populations, which consisted of Danish Caucasians.

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“…The human EG cells resemble mouse EG cells in terms of phenotype, marker expression and pluripotent characteristics (Shamblott et al 1998(Shamblott et al , 2001; however the maintenance of these lines in culture has only been achieved up to 20 passages (Shamblott et al 1998, Turnpenny et al 2003, making their characterisation very difficult. The methylation profile of imprinted genes has thus far only been analysed in human EG cell-differentiated derivatives, because of the impossibility of maintaining the undifferentiated EG cells in culture (Onyango et al 2002). In comparison with derivatives of mouse EG cells derived at 8.5 dpc, human EG cell derivatives from fetuses of 5 -11 weeks post-fertilisation maintained the parental imprinting status, and the authors suggest that the time of imprint erasure differs in the two species.…”

Section: Eg Cellsmentioning

confidence: 99%

Epigenetics and the germline

Allegrucci¹,

Thurston²,

Lucas³

et al. 2005

Reproduction

199

125

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Epigenetic processes affect three stages of germline development, namely (1) specification and formation of primordial germ cells and their germline derivatives through lineage-specific epigenetic modifications, in the same manner as other embryonic lineages are formed, (2) a largely genome-wide erasure and re-establishment of germline-specific epigenetic modifications that only occurs in the embryonic primordial germ cell lineage, followed by re-establishment of sex-specific patterns during gametogenesis, and (3) differential epigenetic modifications to the mature male and female gamete genomes shortly after fertilisation. This review will detail current knowledge of these three processes both at the genome-wide level and at specific imprinted loci. The consequences of epigenetic perturbation are discussed and new in vitro models which may allow further understanding of a difficult developmental period to study, especially in the human, are highlighted.

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Monoallelic expression and methylation of imprinted genes in human and mouse embryonic germ cell lineages

Cited by 61 publications

References 24 publications

Derivation of Human Embryonic Germ Cells: An Alternative Source of Pluripotent Stem Cells

Derivation of Human Embryonic Germ Cells: An Alternative Source of Pluripotent Stem Cells

Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

Epigenetics and the germline

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