Notch signaling is required for maintaining stem-cell features of neuroprogenitor cells derived from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Studies have provided important findings about the roles of Notch signaling in neural development. Unfortunately, however, most of these studies have investigated the neural stem cells (NSCs) of mice or other laboratory animals rather than humans, mainly owing to the difficulties associated with obtaining human brain samples. It prompted us to focus on neuroectodermal spheres (NESs) which are derived from human embryonic stem cell (hESC) and densely inhabited by NSCs. We here investigated the role of Notch signaling with the hESC-derived NESs.</p> <p>Results</p> <p>From hESCs, we derived NESs, the <it>in-vitro </it>version of brain-derived neurospheres. NES formation was confirmed by increased levels of various NSC marker genes and the emergence of rosette structures in which neuroprogenitors are known to reside. We found that Notch signaling, which maintains stem cell characteristics of <it>in-vivo</it>-derived neuroprogenitors, is active in these hESC-derived NESs, similar to their <it>in-vivo </it>counterpart. Expression levels of Notch signaling molecules such as NICD, DLLs, JAG1, HES1 and HES5 were increased in the NESs. Inhibition of the Notch signaling by a γ-secretase inhibitor reduced rosette structures, expression levels of NSC marker genes and proliferation potential in the NESs, and, if combined with withdrawal of growth factors, triggered differentiation toward neurons.</p> <p>Conclusion</p> <p>Our results indicate that the hESC-derived NESs, which share biochemical features with brain-derived neurospheres, maintain stem cell characteristics mainly through Notch signaling, which suggests that the hESC-derived NESs could be an <it>in-vitro </it>model for <it>in-vivo </it>neurogenesis.</p

Interleukin-2 induces the in vitro maturation of human pluripotent stem cell-derived intestinal organoids.

Human pluripotent stem cell (hPSC)-derived intestinal organoids (hIOs) form 3D structures organized into crypt and villus domains, making them an excellent in vitro model system for studying human intestinal development and disease. However, hPSC-derived hIOs still require in vivo maturation to fully recapitulate adult intestine, with the mechanism of maturation remaining elusive. Here, we show that the co-culture with human T lymphocytes induce the in vitro maturation of hIOs, and identify STAT3-activating interleukin-2 (IL-2) as the major factor inducing maturation. hIOs exposed to IL-2 closely mimic the adult intestinal epithelium and have comparable expression levels of mature intestinal markers, as well as increased intestine-specific functional activities. Even after in vivo engraftment, in vitro-matured hIOs retain their maturation status. The results of our study demonstrate that STAT3 signaling can induce the maturation of hIOs in vitro, thereby circumventing the need for animal models and in vivo maturation

Selecting Network-Level Project Sections for Sustainable Pavement Management in Texas

In recent years, the increasing gap between available funding and preservation needs has influenced district pavement engineers to select and prioritize projects to effectively use funding. However, currently, projects are often selected after an informal assessment, based on local conditions and local district engineers’ experience, in the absence of a statewide systematic process. The primary objective of this study is to determine network-level project sections for effective sustainable pavement management using logistic regression analysis. A large volume of inventory data, documented using pavement-management information systems (PMIS), was used to develop the logistic regression (LR) model for selecting candidate sections. The LR model was subsequently validated using a single 50/50 split sample method. The findings of this study will assist the Austin, Texas, USA district to select and evaluate candidate projects. Furthermore, the study will eventually contribute to improved efficiency in project selection and prioritization by reducing not only the amount of time necessary to review the district PMIS data to identify project candidates, but also the potential for human error

Effect of Temperature, pH, and Reaction Duration on Microbially Induced Calcite Precipitation

In this study, the amount of calcite precipitate resulting from microbially induced calcite precipitation (MICP) was estimated in order to determine the optimal conditions for precipitation. Two microbial species (Staphylococcus saprophyticus and Sporosarcina pasteurii) were tested by varying certain parameters such as (1) initial potential of hydrogen (pH) of urea-CaCl2 medium, (2) temperature during precipitation, and (3) the reaction duration. The pH values used for testing were 6, 7, 8, 9, and 10, the temperatures were 20, 30, 40, and 50 &deg;C, and the reaction durations were 2, 3, and 4 days. Maximum calcite precipitation was observed at a pH of 7 and temperature of 30 &deg;C. Most of the precipitation occurred within a reaction duration of 3 days. Under similar conditions, the amount of calcite precipitated by S. saprophyticus was estimated to be five times more than that by S. pasteurii. Both the species were sensitive to temperature; however, S. saprophyticus was less sensitive to pH and required a shorter reaction duration than S. pasteurii

Numerical Analysis of Laterally Loaded Piles Affected by Bedrock Depth

This study investigates the lateral behavior of pile foundations socketed into bedrocks using 3D finite difference analysis. The lateral load-displacement curve, pile deflection, and bending moment distribution were obtained for different bedrock depths between 3 and 20 m. It was discovered that bedrocks that have a depth of 7 m (7D) or less influence the lateral behavior of the pile. The p-y curves were collected at depths of 2.0–4.5 m, and the effect of the bedrock on the curves was evaluated. It was observed that the p-y curves were significantly affected by the material properties of the bedrock if the rock is located in close proximity (within 3D), but the effect is diminished if the p-y curves were 3.5 m (3.5D) or farther from the bedrock

Direct lineage reprogramming to neural cells

Recently we have witnessed an array of studies on direct reprogramming that describe induced inter conversion of mature cell types from higher organisms including human. While these studies reveal an unexpected level of plasticity of differentiated somatic cells, they also provide unprecedented opportunities to develop regenerative therapies for many debilitating disorders and model these 'diseases-in-a-dish' for studying their pathophysiology. Here we review the current state of the art in direct lineage reprogramming to neural cells, and discuss the challenges that need to be addressed toward achieving the full potential of this exciting new technology