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See detailModeling heterogeneity in the pluripotent state: A promising strategy for improving the efficiency and fidelity of stem cell differentiation
Espinosa Angarica, Vladimir UL; del Sol Mesa, Antonio UL

in BioEssays (2016), 38(8),

Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within ... [more ▼]

Pluripotency can be considered a functional characteristic of pluripotent stem cells (PSCs) populations and their niches, rather than a property of individual cells. In this view, individual cells within the population independently adopt a variety of different expression states, maintained by different signaling, transcriptional, and epigenetics regulatory networks. In this review, we propose that generation of integrative network models from single cell data will be essential for getting a better understanding of the regulation of self-renewal and differentiation. In particular, we suggest that the identification of network stability determinants in these integrative models will provide important insights into the mechanisms mediating the transduction of signals from the niche, and how these signals can trigger differentiation. In this regard, the differential use of these stability determinants in subpopulation-specific regulatory networks would mediate differentiation into different cell fates. We suggest that this approach could offer a promising avenue for the development of novel strategies for increasing the efficiency and fidelity of differentiation, which could have a strong impact on regenerative medicine [less ▲]

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See detailShared components of protein complexes--versatile building blocks or biochemical artefacts?
von Mering, Christian; Bork, Peer; Dandekar, Thomas et al

in BioEssays (2004), 26(12), 1333-43

Protein complexes perform many important functions in the cell. Large-scale studies of protein-protein interactions have not only revealed new complexes but have also placed many proteins into multiple ... [more ▼]

Protein complexes perform many important functions in the cell. Large-scale studies of protein-protein interactions have not only revealed new complexes but have also placed many proteins into multiple complexes. Whilst the advocates of hypothesis-free research touted the discovery of these shared components as new links between diverse cellular processes, critical commentators denounced many of the findings as artefacts, thus questioning the usefulness of large-scale approaches. Here, we survey proteins known to be shared between complexes, as established in the literature, and compare them to shared components found in high-throughput screens. We discuss the various challenges to the identification and functional interpretation of bona fide shared components, namely contaminants, variant and megacomplexes, and transient interactions, and suggest that many of the novel shared components found in high-throughput screens are neither the results of contamination nor central components, but appear to be primarily regulatory links in cellular processes. [less ▲]

Detailed reference viewed: 116 (1 UL)
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See detailPax genes and organogenesis.
Dahl, E.; Koseki, H.; Balling, Rudi UL

in BioEssays (1997), 19(9), 755-65

Pax genes are a family of developmental control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA-binding ... [more ▼]

Pax genes are a family of developmental control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA-binding activity. Originally, paired-box-containing genes were detected in Drosophila melanogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), Peter's anomaly (PAX6), renal coloboma syndrome (PAX2) or spontaneous mouse mutants (undulated (Pax1), Splotch (Pax3), Small eye (Pax6), Pax2(1)Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determining the time and place of organ initiation or morphogenesis. For most tissues, however, the nature of the primary developmental action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position-specific regulation of cell proliferation. [less ▲]

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See detailFrom the structure to the function of villin, an actin-binding protein of the brush border.
Friederich, Evelyne UL; Pringault, E.; Arpin, M. et al

in BioEssays (1990), 12(9), 403-8

Villin, a calcium-regulated actin-binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is ... [more ▼]

Villin, a calcium-regulated actin-binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed by transfecting CV1 cells with a human cDNA encoding wild-type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F-actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli. [less ▲]

Detailed reference viewed: 114 (1 UL)