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Epigenetics, Stem cells and Tumorigenicity
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Human Genetics & Embryology

ISSN: 2161-0436

Open Access

Epigenetics, Stem cells and Tumorigenicity

Editorial

Pages: 1 - 3

Toward Live Longer, Younger, Happier and Healthier: Reprogramming for a New Start or Just a Turn?

Yue Zhang Msup

DOI:

DOI: 10.4172/2161-0436.S2-e001

Whether we could live longer, younger, happier, and healthier as well as especially cancer-free in the future? Reprogramming in stem cell therapy and regenerative medicine could shed light on it. Whether the DNA of the mature cell still hold all the information needed to develop all cells in the organism? 50 years ago, most if not all biologists could have said “no.” However, Sir Gurdon applied his frog nuclear tranplantation (cloning) to say “yes”, it thus is feasible with one reprogramming for a new start i.e. the specialisation of cells is reprogrammable. At that time, he even predicted that the mammalian animal cloning would come up during following 50 years. In fact, one of most fascinating events is the Dolly cloning around the turn of this century.

Research Article

Pages: 1 - 11

The Contribution of Next Generation Sequencing Technologies to Epigenome Research of Stem Cell and Tumorigenesis

Jun Li, Tingting Wang, Xiuge Zhang and Xu Yang

DOI:

DOI: 10.4172/2161-0436.S2-001

Epigenome contains another layer of genetic information, not as stable as genome. Dynamic epigenome can serve as an interface to explain the role of environmental factors. Stem cell and tumorigenesis are reported to be closely associated with epigenome modifications. Next generation sequencing (NGS) technologies have directly leaded to the recent advances in epigenome research of stem cell and cancer. DNA methylation and histone modification are two major epigenetic modifications. Four NGS-based approaches have been developed to identify these two epigenetic modifications, including whole genome bisulfite sequencing (WGBS), methylated DNA Immunoprecipitation Sequencing (MeDIP-Seq), reduced representation bisulfite sequencing (RRBS) and chromatin immunoprecipitation sequencing (ChIP-Seq). This paper reviews the recent advances of WGBS, MeDIP-Seq and RRBS for DNA methylation and ChIP-Seq for histone modification in the field of stem cell. The potential contribution of epigenetic modifications to tumorigenesis is also described. At present, the epigenome research still faces the defects of current sampling strategy and unknown network regulation pattern. In future, worldwide collaboration and latest sequencing technologies application are expected to solve these problem and offer new insight into epigenome research.

Review Article

Pages: 1 - 7

Induced Pluripotent Stem Cells: Origins and Directions

Wenjie Jiang, Jian Zhang, Xiaomei Yang and Jiangang Gao

DOI:

DOI: 10.4172/2161-0436.S2-002

Embryonic stem (ES) cells are used in various fields for diverse purposes, including gene targeting, cell therapy, tissue repair, organ regeneration, and so on. However, studies on and applications of ES cells are hindered by ethical disputes regarding cell source. To circumvent ethical issues, scientists have attempted to generate ES celllike cells, which are not derived from the inner cell mass of blastocyst-stage embryos. In 2006, Yamanaka first reprogrammed mouse embryonic fibroblasts into ES cell-like cells, which were called induced pluripotent stem (iPS) cells. Nearly a year later, the Yamanaka and Thomson laboratories independently reprogrammed human somatic cells into iPS cells. Since the establishment of the first iPS cell line, iPS cells have been derived from a number of different cell types and have been used for cell therapy, human disease modeling, and drug discovery. The use of peripheral blood facilitates research on iPS cells and enables the establishment of patient-specific iPS cells. With the improvement in iPS cell technology, clinical therapy based on iPS cells will rapidly develop.

Research Article

Pages: 1 - 7

The Association between the MTR Gene A2576G Polymorphism and Alzheimer?s Disease: a Meta Analysis Study

Yun Wang, Shunliang Xu and Jianzhong Bi

DOI:

DOI: 10.4172/2161-0436.S2-003

Background: Alzheimer’s disease (AD) individuals are characterized with high homocysteine (HCY) and low folate blood levels. Polymorphisms of genes encoding critical enzymes in folate metabolism have been associated with hyperhomocysteinemia and AD risk. An adenine to guanine transition at position 2756 (rs185087) of the methionine synthase (MS or MTR) gene causes hyperhomocysteinemia. However, the association between MTR A2756G polymorphism and AD remains controversial. We performed a Meta analysis pooling data from all relevant studies including cases and controls to reexamine the association between the MTR gene A2576G polymorphism and AD. Methods: We applied random-effects or fixed-effects model according to the degree of heterogeneity to combine odds ratio (OR) and 95% coincidence intervals (95% CI). And we used the Quanto 1.2.4 software to calculate genetic power. Egger’s test was carried out to evaluate the potential publication bias. Results and discussion: Eight case-control studies enrolling 2,880 cases and 2,807 controls were included in this meta analysis. The overall ORs with 95% CIs showed no statistical association between the MTR gene A2756G polymorphism and the risk of AD in the allele contrast, the recessive model or dominant model for allele A (randomeffects pooled OR 1.09, 95% CI 0.92-1.30; random-effects pooled OR 1.11, 95% CI 0.91-1.35; fixed-effects pooled OR 1.13, 95% CI 0.83-1.54, respectively). The genetic power was 11.6% in the recessive model and 43.7% in the dominant model. No association between MTR A2756G polymorphism and AD was observed, but the conclusion based on relatively small numbers of participants. Large heterogeneity was detected among combined populations in the contrast of AA vs. AG+GG (p = 0.019, I2 = 56.3%) and A vs. G (p = 0.016, I2 = 57.5%). One study was considered as the main cause of heterogeneity in both contrasts. The heterogeneity doesn’t reduce in the subgroup analyses stratified by racial descents. It can be presumed that the heterogeneity mainly results from the diagnosis of AD and genotyping methods. No publication bias was observed. Conclusions: In conclusion, the present Meta analysis suggests that MTR A2756G polymorphism is not a genetic determinant of AD. But small sample size may be one reason and it could not be ruled out that a true association exists.

Review Article

Pages: 1 - 8

Epigenetics and Hematopoietic Stem or Progenitor Cells

Yang Wang, Benjamin T. Moore, Xianhao Peng and Peng Xiao

DOI:

DOI: 10.4172/2161-0436.S2-004

The maintenance and differentiation of hematopoietic stem/progenitor cells (HSPCs) is a critical process of hematopoiesis that includes the formation of lymphoid lineage and myeloid lineage. Epigenetic regulation is mainly composed of DNA methylation, histone modifications, non-coding microRNA (miRNA) regulation and chromatin remodeling, which are essential for the maintenance and differentiation of hematopoietic stem/progenitor cells (HSPCs). This review details the epigenetic studies of four major epigenetic mechanisms in normal and aberrant HSPCs, as well as hematopoiesis.

Review Article

Pages: 1 - 6

Umbilical Cord Blood: Medical Waste or Important Source of Stem Cells?

Alexandrina Burlacu

DOI:

DOI: 10.4172/2161-0436.S2-005

The identification of new sources of stem cells may provide significant clinical benefits in the regenerative medicine. Although sometimes still regarded as a medical waste, the blood remained in the umbilical vein after birth (Umbilical Cord Blood, UCB) has become a valuable alternative source of haematopoietic stem cells for the treatment of various disorders. Using UCB is advantageous because it is obtained by a simple, safe and painless procedure when the baby is delivered. The immaturity of UCB cells resulted in a reduced graft-versus-host disease when compared to bone marrow grafts. Furthermore, there may be particular utility in using UCB in the context of HLA mismatch between available donor and recipient. However, due to the limited number of stem cells, the progress in the field has been largely restricted to children. Nevertheless, evidence supporting the efficacy of a double transplant of UCB in adults has significantly increased over the past years, as an alternative to bone marrow transplantation in those adult patients where no compatible donors are available. Today, new parents may choose to have the UCB stored in a stem cell bank. These banks can be public (non-profit) or private (for-profit). The public banks store UCB from donors and provide it when transplantation is prescribed to an unrelated patient. Unfortunately, donation to a public bank is not possible everywhere, although their number is growing. On contrary, the private banks offer a commercial service to parents in order to preserve the UCB for future needs of their child. Storing UCB in such private banks is controversial and recommended only in the case of historical existence of a genetic disease; otherwise the likelihood of stored UCB being used in autologous transplant is negligible. This and other ethical aspects of UCB banking are discussed in this paper.

Research Article

Pages: 1 - 8

Enrichment and Selective Targeting of Cancer Stem Cells in Colorectal Cancer Cell Lines

Shunqi Wang, Deepak Kanojia, Pang-kuo Lo, Varun Chandrashekaran, Xinrui Duan, Franklin G Berger, Qian Wang and Hexin Chen

DOI:

DOI: 10.4172/2161-0436.S2-006

Cancer stem cells (CSCs) are the subpopulation of cells within a tumor proposed to be responsible for tumor initiation, relapses, and resistance to chemotherapeutic drugs. Here we optimized sphere culture conditions to isolate and enrich CSCs from colorectal cancer cell line IMCE-Ras. Spheroid cells that developed in culture expressed high levels of putative stem cell markers, and showed stronger anchorage-independent growth abilities and resistance to conventional chemotherapeutic drugs compared with the initial monolayer adherent cells. Xenograft transplantation assays further demonstrated that IMCE-Ras spheroid cells are highly enriched in CSCs. To develop CSC-targeted therapy, we found that the relative percentage of CSC in IMCE-Ras cells was significantly decreased after a short duration exposure to DNA Methylation inhibitor 5-aza-2’-deoxycytidine (5-Aza-dC), indicating that DNA Methylation may be critical for self-renewal and maintenance of CSCs. Indeed, double knockout of DNA methyltransferase 1 (DNMT1) and DNA methyltransferase 3b (DNMT3b) in colon cancer cell line HCT116 resulted in loss of >95% DNA Methylation and complete loss of tumorigenicity both in vitro and in vivo. These data suggest that DNA Methylation is critical for maintenance of the colon CSC population, and a combination of classical chemotherapeutic drugs and DNA Methylation inhibitors may be an effective treatment of colon cancer.

Review Article

Pages: 1 - 11

Regulation of Mirna Pathway and Roles of Micrornas in Tumorigenesis and Metastasis

Rong Jiang and Yujing Li

DOI:

DOI: 10.4172/2161-0436.S2-007

Although small non-coding RNAs, particularly microRNAs (miRNAs), small interference RNAs (siRNAs), and piwiinteracting RNAs (piRNAs), account for only a minor fraction of the expressed genome, they have been recognized as important regulators of gene and genome at post-transcriptional levels, functioning as RNA interference (RNAi) to regulate some of the most important biological processes in eukaryotic cells. Following the identification of the major components within the RNAi/miRNA pathway, some protein co-factors have been characterized to play significant roles in activity regulation of the RNAi/miRNA pathway in the last few years, suggesting that any regulators must be tightly regulated. It has been shown that microRNAs play vital roles in regulation of multiple signaling pathways and are involved in a variety of physiological and pathological processes. Given that high percentage of the identified human miRNAs-coding genes are located at tumor-related fragile chromosome regions, and that an increasing body of evidence supports the strong link between aberration of miRNA expression and malignancies, the regulatory network organizing the miRNAs, miRNA regulating factors and miRNA targets particularly the tumor suppressors or oncogenes is suggested. This review highlights the current evidence for the significance of the link of miRNAs and tumorigenesis and metastasis.

Google scholar citation report
Citations: 261

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