From endoderm to pancreas: a multistep journey

The formation of the vertebrate pancreas is a complex process that typifies the basic steps of embryonic development. It involves the establishment of competence, specification, signaling from neighboring tissues, morphogenesis, and the elaboration of tissue-specific genetic networks. A full analysis of this multistep process will help us to understand classic principles of embryonic development. Furthermore, this will provide the blueprint for experimental programming of pancreas formation from embryonic stem cells in the context of diabetes cell-therapy. Although in the past decade many studies have contributed to a solid foundation for understanding pancreatogenesis, important gaps persist in our knowledge of early pancreas formation. This review will summarize the current understanding of the early mechanisms coming into play to pattern the "pre-pancreatic" region within the endoderm and, gradually, specify the pancreatic tissue.     

DNA repair mechanisms in embryonic stem cells

Embryonic stem cells (ESCs) can undergo unlimited self-renewal and retain the pluripotency to differentiate into all cell types in the body. Therefore, as a renewable source of various functional cells in the human body, ESCs hold great promise for human cell therapy. During the rapid proliferation of ESCs in culture, DNA damage, such as DNA double-stranded breaks, will occur in ESCs. Therefore, to realize the potential of ESCs in human cell therapy, it is critical to understand the mechanisms how ESCs activate DNA damage response and DNA repair to maintain genomic stability, which is a prerequisite for their use in human therapy. In this context, it has been shown that ESCs harbor much fewer spontaneous mutations than somatic cells. Consistent with the finding that ESCs are genetically more stable than somatic cells, recent studies have indicated that ESCs can mount more robust DNA damage responses and DNA repair than somatic cells to ensure their genomic integrity.     

Generative models: Human embryonic stem cells and multiple modeling relations

Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science.     

Growth ofAedes aegypti embryonic cells and tissues in vitro

Résumé Des tissus et cellules d'embryos d.'Aedes aegypti ont été cultivés dans des milieux de culture pour tissus des insectes contenant aussi le milieu Morgan 199 pour cellules-vertèbres. On peut observer, au commencement du troisième jour, des cellules transparentes nouvelles et formes mitotiques. Les cultures sont restées en bon état pendant plus de trois semaines.     

Increased apoptosis in differentiating p27-deficient mouse embryonic stem cells

In mouse embryonic stem (mES) cells, the expression of p27 is elevated when differentiation is induced. Using mES cells lacking p27 we tested the importance of p27 for the regulation of three critical cellular processes: proliferation, differentiation, and apoptosis. Although cell cycle distribution, DNA synthesis, and the activity of key G1/S-regulating cyclin-dependent kinases remained unaltered in p27-deficient ES cells during retinoic acid-induced differentiation, the amounts of cyclin D2 and D3 in such cells were much lower compared with normal mES cells. The onset of differentiation induces apoptosis in p27-deficient cells, the extent of which can be reduced by artificially increasing the level of cyclin D3. We suggest that the role of p27 in at least some differentiation pathways of mES cells is to prevent apoptosis, and that it is not involved in slowing cell cycle progression. We also propose that the pro-survival function of p27 is realized via regulation of metabolism of D-type cyclin(s).Received 25 February 2004; received after revision 5 April 2004; accepted 15 April 2004     

Stimulation of growth by insulin inDrosophila embryonic cells in vitro

Summary For obtaining a better yield of established lines of embryonicDrosophila cells, insulin proved to be a useful substance to be added to the culture medium. 10% of lines became established, showing a predominatly diploid chromosome number.     

The importance of HLA-G expression in embryos,trophoblast cells,and embryonic stem cells

The nonclassical HLA-G molecule is a trophoblast-specific molecule present in almost every pregnancy. It differs from classical HLA class I molecules by the low degree of allelic variants and the high diversity of protein structures. HLA-G is reported to be a tolerogenic molecule that acts on cells of both innate and adaptive immunity. At the maternal–fetal interface HLA-G seems to be responsible largely for the reprogramming of local maternal immune response. This review will focus on the HLA-G gene expression profile in pregnancy, in preimplantation embryos, and in human embryonic stem cells with emphasis on the structural diversity of the HLA-G protein and its potential functional and diagnostic implications.     

mTOR signaling in neural stem cells: from basic biology to disease

The mammalian target of rapamycin (mTOR) pathway is a central controller of growth and homeostasis, and, as such, is implicated in disease states where growth is deregulated, namely cancer, metabolic diseases, and hamartoma syndromes like tuberous sclerosis complex (TSC). Accordingly, mTOR is also a pivotal regulator of the homeostasis of several distinct stem cell pools in which it finely tunes the balance between stem cell self-renewal and differentiation. mTOR hyperactivation in neural stem cells (NSCs) has been etiologically linked to the development of TSC-associated neurological lesions, such as brain hamartomas and benign tumors. Animal models generated by deletion of mTOR upstream regulators in different types of NSCs reproduce faithfully some of the TSC neurological alterations. Thus, mTOR dysregulation in NSCs seems to be responsible for the derangement of their homeostasis, thus leading to TSC development. Here we review recent advances in the molecular dissection of the mTOR cascade, its involvement in the maintenance of stem cell compartments, and in particular the implications of mTOR hyperactivation in NSCs in vivo and in vitro.     

Morphological effects of concanavalin A on amphibian embryonic cells differentiating in vitro (author's transl)]

Concanavalin A exerts an irreversible inhibitory effect on the differentiation of cultured embryonic amphibians cells in vitro. Cytological changes and distrubances of cell attachment, and spreading to the culture support occur in parallel. Polykaryons have been noticed in treated cultures.     

Susceptibility of chick neural retina to viral multiplication in vitro during embryonic development

Decrease in the susceptibility of embryonic chick neural retina cultures to the multiplication of various viruses was observed with increasing age of the embryo. In contrast the retinal cells supported the multiplication of Sindbis virus irrespective of the age when they were infected with the viral RNA. These results suggest that the restricted multiplication of the viruses observed is due to the modulated inability of the cell to process the adsorbed viruses for subsequent replication.     

Susceptibility of chick neural retina to viral multiplication in vitro during embryonic development

Summary Decrease in the susceptibility of embryonic chick neural retina cultures to the multiplication of various viruses was observed with increasing age of the embryo. In contrast the retinal cells supported the multiplication of Sindbis virus irrespective of the age when they were infected with the viral RNA. These results suggest that the restricted multiplication of the viruses observed is due to the modulated inability of the cell to process the adsorbed viruses for subsequent replication.