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Embryonic stem cells have the ability to differentiate into nearly all cell types. However, the molecular mechanism of its pluripotency is still unclear. Oct3/4, Sox2 and Nanog are important factors of pluripotency. Oct3/4 (hereafter referred to as Oct4), in particular, has been an irreplaceable factor in the induction of pluripotency in adult cells. Proteins interacting with Oct4 and Nanog have been identified via affinity purification and mass spectrometry. These data, together with iterative purifications of interacting proteins allowed a protein interaction network to be constructed. The network currently includes 77 transcription factors, all of which are interconnected in one network. In-depth studies of some of these transcription factors show that they all recruit the NuRD complex. Hence, transcription factor clustering and chromosomal remodeling are key mechanism used by embryonic stem cells. Studies using RNA interference suggest that more pluripotency genes are yet to be discovered via protein-protein interactions. More work is required to complete and curate the embryonic stem cell protein interaction network. Analysis of a saturated protein interaction network by system biology tools can greatly aid in the understanding of the embryonic stem cell pluripotency network.

The derivation of human ES cells (hESCs) from human blastocysts represents one of the milestones in stem cell biology (1). The full potential of hESCs in research and clinical applications [...]

Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells (1). The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies., The pluripotency and self-renewing properties of ESCs are conferred by a set of core factors that helps determine their unique identity. Adult somatic cells can be reprogrammed to resemble ESCs [...]

Objective(s): The involvement of tetratricopeptide repeat domain 9A (TTC9A) in anxiety-like behaviors through estrogen action has been reported in female mice, this study further investigated its effects on social anxiety and aggressive behaviors. Materials and Methods: Using female Ttc9a knockout (Ttc9a-/-) mice, the role of TTC9A in anxiety was investigated in non-social and social environments through home-cage emergence and social interaction tests, respectively, whereas aggressive behaviors were examined under the female intruder test. Results: We observed significant social behavioral deficits with pronounced social and non-social anxiogenic phenotypes in female Ttc9a-/-mice. When tested for aggressive-like behaviors, we found a reduction in offense in Ttc9a-/-animals, suggesting that TTC9A deficiency impairs the offense responses in female mice. Conclusion: Future study investigating mechanisms underlying the social anxiety-like behavioral changes in Ttc9a-/-mice may promote the understanding of social and anxiety disorders. [ABSTRACT FROM AUTHOR]

Research has been conducted on the role of the mammalian Dlx homeobox genes in limb development. Results indicate that the targeted disruption of these genes has led to the bone, inner ear and craniofacial defects.

A study disrupted the entire gene or the isoform retinoic acid receptor alpha 1 (RARalpha1) in the mouse to explore the role of the RARalpha gene. The regular growth and maintenance of some tissues depends heavily on retinoic acid (RA). The three nuclear receptors RARalpha, -beta, and -gamma, are each as multiple isoforms, and believed to partially mediate the action of RA. RARalpha1-null mice seemed normal though RARalpha1 is the main isoform and is extremely conserved among vertebrates. Early postnatal lethality and testis degeneration resulted from targeted disruption of the entire RARalpha gene. Genetic redundancy cannot be ruled out, and RARalpha is definitely concerned with the transduction of the RA signal.

The disruption of the Hox gene in mice causes the occipital bones of the skull to develop abnormally but only in regions anterior to the gene's usual area of expression. The ectopic expression of Hox 4.2 induces a homeotic alteration of the occipital bones into a posterior phenotype similar in shape to the cervical vertebrae. However, no such change affects structures ordinarily controlled by Hox 4.2. Thus, it is manifest that posterior Hox genes can reconfigure anterior skeletal arrangements.