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71.
Faherty S Fitzgerald A Keohan M Quinlan LR 《In vitro cellular & developmental biology. Animal》2007,43(1):37-47
In this study we examined the role of the cAMP/protein kinase A (PKA) pathway in affecting IOUD2 ES cell self-renewal and
differentiation, Oct4 expression, and cell proliferation. Forskolin, the adenylate cyclase agonist, alone had no effect on
ES cell self-renewal. However, when cells were treated with the differentiation-inducing agent retinoic acid, forskolin significantly
promoted ES cell self-renewal. Effectively, forskolin rescued cells from a pathway of differentiation. Culturing ES cells
in the presence of the phosphodiesterase inhibitor IBMX had no effect on ES cell self-renewal but did increase cell proliferation.
In the presence of 100 μM IBMX without LIF, 10 μM forskolin significantly increased ES cell self-renewal. The cell permeable
cAMP analog 8-Br-cAMP (1 and 5 mM) promoted ES cell differentiation in the presence of LIF, while in the absence of LIF, it
promoted ES cell self-renewal. The effect of the PKA specific inhibitors H89 and KT5720 on Oct4 expression was, again, LIF-dependent.
In the presence of LIF, these inhibitors decreased Oct4 expression, while they increased Oct4 expression in the absence of
LIF. In general, ES cells maintained on a self-renewal pathway through the presence of LIF show little effect from altered
cAMP signaling except at higher levels. However, in strict contrast, when ES cell are on a differentiation pathway through
exposure to retinoic acid or the removal of LIF, altering cAMP levels can rescue the self-renewal process promoting Oct4 expression.
This study clearly shows that the cAMP/PKA pathway plays a role in ES cell self-renewal pathways.
This work was partly funded by the Millennium Research Fund National University of Ireland Galway. 相似文献
72.
Ewelina Elert-Dobkowska J. Christopher Hennings Christian A. Hübner Christian Beetz 《Analytical biochemistry》2015
Following locus-specific genome editing of mouse embryonic stem cells (ESCs), the identification of correctly targeted clones remains a challenge. We applied multiplex ligation-dependent probe amplification (MLPA) to screen for homologous recombination-based genomic integration of a knockout construct in which part of a gene is deleted. All candidate ESCs thereby identified were subsequently validated by conventional methods. Thus, MLPA represents a highly reliable as well as cost- and time-efficient alternative to currently applied methods such as Southern blotting and polymerase chain reaction (PCR)-based approaches. It is also applicable to knockin recombination strategies and compatible with the CRISPR/Cas9 system and other genome editing strategies. 相似文献
73.
74.
Hubert Pausch Hermann Schwarzenbacher Johann Burgstaller Krzysztof Flisikowski Christine Wurmser Sandra Jansen Simone Jung Angelika Schnieke Thomas Wittek Ruedi Fries 《BMC genomics》2015,16(1)
Background
Cattle breeding populations are susceptible to the propagation of recessive diseases. Individual sires generate tens of thousands of progeny via artificial insemination. The frequency of deleterious alleles carried by such sires may increase considerably within few generations. Deleterious alleles manifest themselves often by missing homozygosity resulting from embryonic/fetal, perinatal or juvenile lethality of homozygotes.Results
A scan for homozygous haplotype deficiency in 25,544 Fleckvieh cattle uncovered four haplotypes affecting reproductive and rearing success. Exploiting whole-genome resequencing data from 263 animals facilitated to pinpoint putatively causal mutations in two of these haplotypes. A mutation causing an evolutionarily unlikely substitution in SUGT1 was perfectly associated with a haplotype compromising insemination success. The mutation was not found in homozygous state in 10,363 animals (P = 1.79 × 10−5) and is thus likely to cause lethality of homozygous embryos. A frameshift mutation in SLC2A2 encoding glucose transporter 2 (GLUT2) compromises calf survival. The mutation leads to premature termination of translation and activates cryptic splice sites resulting in multiple exon variants also with premature translation termination. The affected calves exhibit stunted growth, resembling the phenotypic appearance of Fanconi-Bickel syndrome in humans (OMIM 227810), which is also caused by mutations in SLC2A2.Conclusions
Exploiting comprehensive genotype and sequence data enabled us to reveal two deleterious alleles in SLC2A2 and SUGT1 that compromise pre- and postnatal survival in homozygous state. Our results provide the basis for genome-assisted approaches to avoiding inadvertent carrier matings and to improving reproductive and rearing success in Fleckvieh cattle.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1483-7) contains supplementary material, which is available to authorized users. 相似文献75.
76.
A BAC transgenic Hes1-EGFP reporter reveals novel expression domains in mouse embryos 总被引:1,自引:0,他引:1
Klinck R Füchtbauer EM Ahnfelt-Rønne J Serup P Jensen JN Jørgensen MC 《Gene expression patterns : GEP》2011,11(7):415-426
Expression of the basic helix-loop-helix factor Hairy and Enhancer of Split-1 (Hes1) is required for normal development of a number of tissues during embryonic development. Depending on context, Hes1 may act as a Notch signalling effector which promotes the undifferentiated and proliferative state of progenitor cells, but increasing evidence also points to Notch independent regulation of Hes1 expression. Here we use high resolution confocal scanning of EGFP in a novel BAC transgenic mouse reporter line, Tg(Hes1-EGFP)1Hri, to analyse Hes1 expression from embryonic day 7.0 (e7.0). Our data recapitulates some previous observations on Hes1 expression and suggests new, hitherto unrecognised expression domains including expression in the definitive endoderm at early somite stages before gut tube closure and thus preceding organogenesis. This mouse line will be a valuable tool for studies addressing the role of Hes1 in a number of different research areas including organ specification, development and regeneration. 相似文献
77.
生殖细胞的发生是发育和遗传的基础。在几乎所有哺乳动物中,原始生殖细胞(primordial germ cell,PGC)均由近端上胚层体细胞在周边细胞特定的信号诱导下特化而成。目前的研究已经发现一些与生殖细胞特化有关的信号分子和关键转录调控元件,以及特化后生殖细胞获得的与体细胞不同的生物特性。生殖细胞的特化是一个结合了体细胞发育程序的抑制、细胞多能性程序的启动和全基因组表观遗传重编程三个方面的动态的复杂过程。多能性干细胞(胚胎干细胞或诱导型多能干细胞)具有发育全能性,能分化为机体任何一种细胞类型,包括生殖细胞。利用多能性干细胞体外分化形成生殖细胞有助于深入系统地研究配子发生的调控机制,为干细胞在不育症治疗方面的应用带来新希望。 相似文献
78.
DPPA2(Developmental pluripotency.associatedgene2)是近年来发现的一种在多能性细胞和某些癌组织中特意表达的基因。它与早期胚胎发育密切相关,参与维持胚胎干细胞的多能性及自我更新,还在体细胞重编程为多能性诱导干细胞的过程中发挥了作用。此外,它还是一种新的肿瘤抗原,有望成为某些恶性肿瘤的特异性免疫治疗新靶点。本文就DPPA2的结构、功能,以及它与胚胎发育、恶性肿瘤、体细胞重编程的关系等方面的研究进展做一综述。 相似文献
79.
Ada Ao Charles H. Williams Jijun Hao Charles C. Hong 《Journal of visualized experiments : JoVE》2011,(50)
Differentiation of pluripotent stem cells is tightly controlled by temporal and spatial regulation of multiple key signaling pathways. One of the hurdles to its understanding has been the varied methods in correlating changes of key signaling events to differentiation efficiency. We describe here the use of a mouse embryonic stem (ES) cell based assay to identify critical time windows for Wnt/β-catenin and BMP signal activation during cardiogenic induction. By scoring for contracting embryonic bodies (EBs) in a 96-well plate format, we can quickly quantify cardiogenic efficiency and identify crucial time windows for Wnt/β-catenin and BMP signal activation in a time course following specific modulator treatments. The principal outlined here is not limited to cardiac induction alone, and can be applied towards the study of many other cell lineages. In addition, the 96-well format has the potential to be further developed as a high throughput, automated assay to allow for the testing of more sophisticated experimental hypotheses. 相似文献
80.