Endothelial basement membrane limits tip cell formation by inducing Dll4/Notch signalling in vivo

How individual components of the vascular basement membrane influence endothelial cell behaviour remains unclear. Here we show that laminin α4 (Lama4) regulates tip cell numbers and vascular density by inducing endothelial Dll4/Notch signalling in vivo. Lama4 deficiency leads to reduced Dll4 expression, excessive filopodia and tip cell formation in the mouse retina, phenocopying the effects of Dll4/Notch inhibition. Lama4-mediated Dll4 expression requires a combination of integrins in vitro and integrin β1 in vivo. We conclude that appropriate laminin/integrin-induced signalling is necessary to induce physiologically functional levels of Dll4 expression and regulate branching frequency during sprouting angiogenesis in vivo

Laminin isoforms in human embryonic stem cells : synthesis, receptor usage and growth support

Sanna Vuoristo, Ismo Virtanen, Minna Takkunen, Jaan Palgi, Yamato Kikkawa, Patricia Rousselle, Kiyotoshi Sekiguchi, Timo Tuuri, and Timo Otonkoski, "Laminin isoforms in human embryonic stem cells: synthesis, receptor usage and growth support", Journal of Cellular and Molecular Medicine, 13, 8b, pp. 2622-2633, Wiley, 200

Recombinant Laminins Drive the Differentiation and Self-Organization of hESC-Derived Hepatocytes

SummaryStem cell-derived somatic cells represent an unlimited resource for basic and translational science. Although promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes that are the product of using undefined components in the differentiation process. This serves as a significant barrier to scale-up and application. To tackle this issue, we designed a defined differentiation process using recombinant laminin substrates to provide instruction. We demonstrate efficient hepatocyte specification, cell organization, and significant improvements in cell function and phenotype. This is driven in part by the suppression of unfavorable gene regulatory networks that control cell proliferation and migration, pluripotent stem cell self-renewal, and fibroblast and colon specification. We believe that this represents a significant advance, moving stem cell-based hepatocytes closer toward biomedical application

<i>Ochotopteris</i>—An Endemic Fern of the Mid-Cretaceous Arctic

Three species belonging to the fern genus Ochotopteris E. Lebedev, including the new species O. lebedevii Herman et Domogatskaya, are revised, described and illustrated in this paper. The fossils come from Albian, Cenomanian, Turonian and Coniacian beds exposed at seven sites in North-Eastern Asia and Northern Alaska. These sites are located in the Cretaceous Arctic, with their palaeolatitudes ranging from 60° N to 80° N. The high endemism characteristic of the mid-Cretaceous Arctic flora is most probably due to adaptations in the globally distinctive Arctic conditions: the unique combination of temperatures, precipitation and the highly seasonal polar light regime. Being an endemic plant of the mid-Cretaceous Arctic, Ochotopteris ferns were adapted to a regional wet temperate to a wet warm temperate palaeoclimate accompanied by marked sunlight seasonality with a prolonged—up to several weeks—winter darkness and continuous summer daylight, also lasting for several weeks. The majority of the mid-Cretaceous Arctic plants were deciduous. Their predominant deciduousness was most probably due to the polar light seasonality: at the end of the growing season, some plants dropped their leaves or leafy shoots, whereas others—including Ochotopteris ferns—died back to rhizome systems

The composition of the middle Miocene (15 Ma) Namling paleoflora, South Central Tibet, in the context of other Tibetan and Himalayan Floras

Molecular phylogeneticists often find that a diversification of western Chinese plant taxa took place in the Miocene and link this to the Neogene uplift of the Tibetan Plateau. This link is made despite abundant geological evidence showing that a high but topographically complex Tibet already existed in the Paleogene. To evaluate and constrain molecular phylogenetic trees and better understand Asian plant diversification requires accurate systematic assignment of well-dated plant megafossils. Here, as part of an ongoing programme of absolute dating and taxonomic evaluation of fossil floras across southwestern China and the Himalaya, we present a new and expanded systematic treatment of the late Miocene leaf flora from the Gazhacun Formation near the village of Wang b'dui in Namling County, central southern Tibet. This flora, whose age (15 Ma) and paleoelevation (~ 5 km) are well constrained, comprises 9 families, 13 genera and 25 species (including 22 new species). The paleoflora represents a typical boreal temperate mostly deciduous broad-leaved forest attesting to a cool humid climate. At the paleolatitude of the site, < 28 °N, this is compatible with the high elevation (4700–5200 m) for this part of Tibet quantified by both leaf physiognomy and isotopic analyses. Plant fossil evidence also witnesses a much wetter Tibetan upland environment before a rising Himalaya obstructed northward-moving moist air from the Indian Ocean

Physical, Spatial, and Molecular Aspects of Extracellular Matrix of In Vivo Niches and Artificial Scaffolds Relevant to Stem Cells Research

Extracellular matrix can influence stem cell choices, such as self-renewal, quiescence, migration, proliferation, phenotype maintenance, differentiation, or apoptosis. Three aspects of extracellular matrix were extensively studied during the last decade: physical properties, spatial presentation of adhesive epitopes, and molecular complexity. Over 15 different parameters have been shown to influence stem cell choices. Physical aspects include stiffness (or elasticity), viscoelasticity, pore size, porosity, amplitude and frequency of static and dynamic deformations applied to the matrix. Spatial aspects include scaffold dimensionality (2D or 3D) and thickness; cell polarity; area, shape, and microscale topography of cell adhesion surface; epitope concentration, epitope clustering characteristics (number of epitopes per cluster, spacing between epitopes within cluster, spacing between separate clusters, cluster patterns, and level of disorder in epitope arrangement), and nanotopography. Biochemical characteristics of natural extracellular matrix molecules regard diversity and structural complexity of matrix molecules, affinity and specificity of epitope interaction with cell receptors, role of non-affinity domains, complexity of supramolecular organization, and co-signaling by growth factors or matrix epitopes. Synergy between several matrix aspects enables stem cells to retain their function in vivo and may be a key to generation of long-term, robust, and effective in vitro stem cell culture systems