《干细胞》：滋养层干细胞重编程研究获进展

来自北京生命科学研究所的研究人员于2月8日在《干细胞》（Stem Cells）杂志上发表了题为 ＂Reprogramming of trophoblast stem cells into pluripotent stem cells by Oct4＂ 的新研究文章。该文章首次报道了一个转录因子Oct4可以将滋养外胚层来源的滋养层干细胞重编程为具有分化为三胚层能力的多潜能干细胞。     

Second intron of mouse nestin gene directs its expression in pluripotent embryonic carcinoma cells through POU factor binding site

Nestin,an intermediate filament protein,is expressed in the neural stem cells of the developingcentral nervous system.This tissue-specific expression is driven by the neural stem cell-specific enhancer inthe second intron of the nestin gene.In this study,we showed that the mouse nestin gene was expressed inpluripotent embryonic carcinoma (EC) P19 and F9 cells,not in the differentiated cell types.This cell type-specific expression was conferred by the enhancer in the second intron.Mutation of the conserved POUfactor-binding site in the enhancer abolished the reporter gene expression in EC cells.Oct4,a Class V POUfactor,was found to be coexpressed with nestin in EC cells.Electrophoretic mobility-shift assays and supershiftassays showed that a unique protein-DNA complex was formed specifically with nuclear extracts of ECcells,and Oct4 protein was included.Together,these results suggest the functional relevance between theconserved POU factor-binding site and the expression of the nestin gene in pluripotent EC cells.     

Advances in cellular technology in the hematology field: What have we learned so far?

Despite the advances in the hematology field, blood transfusion-related iatrogenesis is still a major issue to be considered during such procedures due to blood antigenic incompatibility. This places pluripotent stem cells as a possible ally in the production of more suitable blood products. The present review article aims to provide a comprehensive summary of the state-of-theart concerning the differentiation of both embryonic stem cells and induced pluripotent stem cells to hematopoietic cell lines. Here, we review the most recently published protocols to achieve the production of blood cells for future application in hemotherapy, cancer therapy and basic research.     

Cell signalling pathways underlying induced pluripotent stem cell reprogramming

Induced pluripotent stem(i PS) cells, somatic cells reprogrammed to the pluripotent state by forced expression of defined factors, represent a uniquely valuable resource for research and regenerative medicine. However, this methodology remains inefficient due to incomplete mechanistic understanding of the reprogramming process. In recent years, various groups have endeavoured to interrogate the cell signalling that governs the reprogramming process, including LIF/STAT3, BMP, PI3 K, FGF2, Wnt, TGFβ and MAPK pathways, with the aim of increasing our understanding and identifying new mechanisms of improving safety, reproducibility and efficiency. This has led to a unified model of reprogramming that consists of 3 stages: initiation, maturation and stabilisation. Initiation of reprogramming occurs in almost all cells that receive the reprogramming transgenes; most commonly Oct4, Sox2, Klf4 and c Myc, and involves a phenotypic mesenchymal-to-epithelial transition. The initiation stage is also characterised by increased proliferation and a metabolic switch from oxidative phosphorylation to glycolysis. The maturation stage is considered the major bottleneck within the process, resulting in very few "stabilisation competent" cells progressing to the final stabilisation phase. To reach this stage in both mouse and human cells, pre-i PS cells must activate endogenous expression of the core circuitry of pluripotency, comprising Oct4, Sox2, and Nanog, and thus reach a state of transgene independence. By the stabilisation stage, i PS cells generally use the same signalling networks that govern pluripotency in embryonic stem cells. These pathways differ between mouse and human cells although recent work has demonstrated that this is context dependent. As i PS cell generation technologies move forward, tools are being developed to interrogate the process in more detail, thus allowing a greater understanding of this intriguing biological phenomenon.     

From stem cells to red blood cells:how far away from the clinical application?

The generation of red blood cells(RBCs)from stem cells provides a solution for deficiencies in blood transfusion.Currently,primary hematopoietic stem cells,embryonic stem cells and induced pluripotent stem cells have shown the potential to produce fully mature RBCs.Here,we discuss the advantages,induction protocols,progress and possible clinical applications of stem cells in RBC production.     

Call for Papers Special Issue on "Induced Pluripotent Stem Cells"

The journal Genomics Proteomics & Bioinformatics (GPB) is now inviting submissions for a special issue (to be published around October in 2013) on the topic of "Induced Pluripotent Stem Cells". The induced pluripotent stem cells (iPSCs) are a type of pluripotent stem cells artificially derived from non-pluripotent cells, typically adult somatic cells     

The early human germ cell lineage does not express SOX2 during in vivo development or upon in vitro culture

NANOG, POU5F1, and SOX2 are required by the inner cell mass of the blastocyst and act cooperatively to maintain pluripotency in both mouse and human embryonic stem cells. Inadequacy of any one of them causes loss of the undifferentiated state. Mouse primordial germ cells (PGCs), from which pluripotent embryonic germ cells (EGCs) are derived, also express POU5F1, NANOG, and SOX2. Thus, a similar expression profile has been predicted for human PGCs. Here we show by RT-PCR, immunoblotting, and immunohistochemistry that human PGCs express POU5F1 and NANOG but not SOX2, with no evidence of redundancy within the group B family of human SOX genes. Although lacking SOX2, proliferative human germ cells can still be identified in situ during early development and are capable of culture in vitro. Surprisingly, with the exception of FGF4, many stem cell-restricted SOX2 target genes remained detected within the human SOX2-negative germ cell lineage. These studies demonstrate an unexpected difference in gene expression between human and mouse. The human PGC is the first primary cell type described to express POU5F1 and NANOG but not SOX2. The data also provide a new reference point for studies attempting to turn human stem cells into gametes by normal developmental pathways for the treatment of infertility.