Reprogramming of somatic cells to a pluripotent embryonic stem cell‐like state has been achieved by nuclear transplantation of a somatic nucleus into an enucleated egg and most recently by ...introducing defined transcription factors into somatic cells. Nuclear reprogramming is of great medical interest as it has the potential to generate a source of patient‐specific cells. This short review summarizes strategies to reprogram somatic cells to a pluripotent embryonic state and discuss the implications of this technology for transplantation medicine.
Cloning of mammals by nuclear transfer (NT) results in gestational or neonatal failure with at most a few percent of manipulated embryos resulting in live births. Many of those that survive to term ...succumb to a variety of abnormalities that are likely due to inappropriate epigenetic reprogramming. Cloned embryos derived from donors, such as embryonic stem cells, that may require little or no reprogramming of early developmental genes develop substantially better beyond implantation than NT clones derived from somatic cells. Although recent experiments have demonstrated normal reprogramming of telomere length and X chromosome inactivation, epigenetic information established during gametogenesis, such as gametic imprints, cannot be restored after nuclear transfer. Survival of cloned animals to birth and beyond, despite substantial transcriptional dysregulation, is consistent with mammalian development being rather tolerant to epigenetic abnormalities, with lethality resulting only beyond a threshold of faulty gene reprogramming encompassing multiple loci.
Mouse embryonic stem cells (mESCs) have the ability to differentiate into any cell type and can generate chimeric mice when transplanted into a host blastocyst. This remarkable potential, together ...with the development of robust gene targeting strategies in mESCs, were essential for establishing the mouse as the most widely used model organism in biomedical research. Recent advances have allowed the isolation of human embryonic stem cells and the derivation of induced pluripotent stem cells. Genetic tools similar to those proven routine in the mouse system are needed to realize the full potential of human pluripotent cells as disease models and putative therapeutics. Gene targeting in human cells, however, has proven to be more difficult, more time-consuming, and less robust than in mESCs. In this chapter, we discuss the strategies that have been used to allow specific genetic modifications in human pluripotent cells. We focus on the novel application of custom-engineered zinc-finger nucleases for gene targeting, which has promise to become a robust tool for efficient genetic manipulation of human pluripotent cells.
Endothelial dysfunction plays as an important role on mismatch responses that occur during exercise in patients with congestive heart failure (CHF). However, cardiac rehabilitation, a core component ...of management of CHF patients, can improve endothelial function, contributing to reduce the morbidity and mortality of these patients. The primary aims of this review were to describe the importance of flow-mediated dilatation (FMD) as a non-invasive validation tool to assess endothelial dysfunction and to highlight the relevance of scientific studies that evaluated the effects of exercise interventions on peripheral vascular endothelial function as measured by FMD in patients with CHF with both preserved and reduced ejection fraction.
Epigenetic Instability in ES Cells and Cloned Mice Humpherys, David; Eggan, Kevin; Akutsu, Hidenori ...
Science (American Association for the Advancement of Science),
07/2001, Letnik:
293, Številka:
5527
Journal Article
Recenzirano
Cloning by nuclear transfer (NT) is an inefficient process in which most clones die before birth and survivors often display growth abnormalities. In an effort to correlate gene expression with ...survival and fetal overgrowth, we have examined imprinted gene expression in both mice cloned by nuclear transfer and in the embryonic stem (ES) cell donor populations from which they were derived. The epigenetic state of the ES cell genome was found to be extremely unstable. Similarly, variation in imprinted gene expression was observed in most cloned mice, even in those derived from ES cells of the same subclone. Many of the animals survived to adulthood despite widespread gene dysregulation, indicating that mammalian development may be rather tolerant to epigenetic aberrations of the genome. These data imply that even apparently normal cloned animals may have subtle abnormalities in gene expression.
•We quantified the yield benefits of fungicide to wheat using plot and survey data.•Fungicide yield benefits (7.8 ± 15 %) were greater in wetter growing seasons.•Susceptible genotypes benefited more ...from fungicides (17 %) than resistant ones (6 %).•Fungicides improved stability and modified environment-adaptability of genotypes.•Fungicide yield benefits were greater (31 %) in the survey data.
Foliar fungicides can account for a large portion of the yield gap in winter wheat (Triticum aestivum L.); however, their impacts on yield have been inconsistent in rainfed environments. We compiled a database of replicated field experiments and producer-reported fungicide and yield data from commercial fields to quantify the effects of fungicide application on winter wheat yield and yield stability. The database of field experiments (i.e., canopy level) included 56 non-inoculated environments spanning 12 growing seasons in eight Kansas locations, and was restricted to field experiments with direct comparisons between a foliar fungicide between Zadoks 40–55 and a side-by-side untreated control, resulting in 393 mean yield comparisons resulting from 3226 yield observations. The producer survey included genotype and fungicide management data from 654 commercial Kansas wheat fields cultivated across three growing seasons. Grain yield and weather conditions in the experimental and producer-reported database were similar, with seasonal precipitation ranging from ˜150 to 1035 mm and average grain yield of ˜3900 kg ha−1 with a ˜7000 kg ha−1 range. Foliar fungicide application resulted in 7.8 % average yield gain in the canopy-level data, ranging from −27 % to +97 %. Yield differences due to fungicide were strongly related to precipitation and to the ratio of precipitation and reference evapotranspiration (WS:WD) during the spring in the experimental data. Grain yield responsiveness to fungicide associated with the responsiveness of green canopy cover, kernel weight, biomass, and harvest index. Analysis of covariance suggested that grain yield usually decreased with increases in disease susceptibility in the absence of foliar fungicides; however, yield-disease relationships were either neutral or positive in the presence of fungicides. Average yield gain for resistant varieties was ˜166 kg ha−1 (5.6 %), which was lower than for intermediate (˜199 kg ha−1; 6.9 %) or susceptible genotypes (˜598 kg ha−1; 16.9 %). Foliar fungicides increased yield stability across genotypes at the canopy level and at the commercial field level. In the commercial-field level data, 53 % of the fields received foliar fungicide, with higher frequency in growing seasons with greater WS:WD (which were also higher yielding). The use of foliar fungicides was associated with improved yields and interacted with genotype’s resistance level to stripe rust and with growing seasons’ WS:WD. This work quantified and explained the yield benefits of foliar fungicide, and characterized its dependency on genotype-specific disease resistance and environmental conditions both at the canopy- and commercial field-levels.
The successes in animal cloning suggest to some that the technology has matured sufficiently to justify its application to human cloning. There are many social and ethical reasons why the authors ...would never be in favor of copying a person.
Expression of the Xist gene, a key player in mammalian X inactivation, has been proposed to be controlled by the antisense Tsix transcript. Targeted deletion of the Tsix promoter encompassing the ...DPXas34 locus leads to nonrandom inactivation of the mutant X, but it remains unresolved whether this phenotype is caused by loss of Tsixtranscription or by deletion of a crucial DNA element. In this study we determined the role of Tsix transcription in random X inactivation by using mouse embryonic stem (ES) cells as a model system. Two approaches were chosen to modulate Tsixtranscription with minimal disturbance of genomic sequences. First, Tsix transcription was functionally inhibited by introducing a transcriptional stop signal into the transcribed region of Tsix. In the second approach, an inducible system forTsix expression was created. We found that the truncation of the Tsix transcript led to complete nonrandom inactivation of the targeted X chromosome. Induction of Tsix transcription during ES cell differentiation, on the other hand, caused the targeted chromosome always to be chosen as the active chromosome. These results for the first time establish a function for antisense transcription in the regulation of X inactivation.
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