A Network of microRNAs Acts to Promote Cell Cycle Exit and Differentiation of Human Pancreatic Endocrine Cells.

Pancreatic endocrine cell differentiation is orchestrated by the action of transcription factors that operate in a gene regulatory network to activate endocrine lineage genes and repress lineage-inappropriate genes. MicroRNAs (miRNAs) are important modulators of gene expression, yet their role in endocrine cell differentiation has not been systematically explored. Here we characterize miRNA-regulatory networks active in human endocrine cell differentiation by combining small RNA sequencing, miRNA over-expression, and network modeling approaches. Our analysis identified Let-7g, Let-7a, miR-200a, miR-127, and miR-375 as endocrine-enriched miRNAs that drive endocrine cell differentiation-associated gene expression changes. These miRNAs are predicted to target different transcription factors, which converge on genes involved in cell cycle regulation. When expressed in human embryonic stem cell-derived pancreatic progenitors, these miRNAs induce cell cycle exit and promote endocrine cell differentiation. Our study delineates the role of miRNAs in human endocrine cell differentiation and identifies miRNAs that could facilitate endocrine cell reprogramming

Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12

No abstract available.The pro-Th2 cytokine IL-33 is now emerging as an important Th1 cytokine-IFN-γ inducer in murine CD4+ T cells that is essential for protective cell-mediated immunity against viral infection in mice. However, whether IL-33 can promote human Th1 cell differentiation and how IL-33 polarizes Th1 cells is less understood. We assessed the ability of IL-33 to induce Th1 cell differentiation and IFN-γ production in vitro and in vivo. We report here that IL-33 alone had no ability in Th1 cell polarization. However it potentiated IL-12-mediated Th1 cell differentiation and IFN-γ production in TCR-stimulated murine and human CD4+ T cells in vitro and in vivo. IL-33 promoted Th1 cell development via MyD88 and synergized with IL-12 to enhance St2 and IL-12R expression in CD4+ T cells. These data therefore provide a novel mechanism for Th1 cell differentiation and optimal induction of a Type 1 response. Thus, IL-33 is capable of inducing IL-12-dependent Th1 cell differentiation in human and mouse CD4+ T cells

Ratio control in a cascade model of cell differentiation

We propose a kind of reaction-diffusion equations for cell differentiation, which exhibits the Turing instability. If the diffusivity of some variables is set to be infinity, we get coupled competitive reaction-diffusion equations with a global feedback term. The size ratio of each cell type is controlled by a system parameter in the model. Finally, we extend the model to a cascade model of cell differentiation. A hierarchical spatial structure appears as a result of the cell differentiation. The size ratio of each cell type is also controlled by the system parameter.Comment: 13 pages, 7 figure

Compositions comprising citrate and applications thereof

In one aspect, methods of promoting bone growth are described herein. In some embodiments, a method of promoting bone growth described herein comprises promoting cell differentiation or phenotype progression in a population of bone cells by providing a citrate-presenting composition to the population of bone cells. In some embodiments, the citrate-presenting composition is provided to the bone cells at a first stage of cell development selected to obtain a first cell differentiation or phenotype progression. Additionally, in some cases, a second citrate-presenting composition is further provided to the bone cells at a second stage of cell development selected to obtain a second cell differentiation or phenotype progression.Board of Regents, University of Texas Syste

Angiogenesis: A Model of Cell Differentiation

Angiogenesis is the formation of blood vessels, and is of great importance in the growth of tumours. Attempts have been made to desgin experiments in petri-dishes that mimic the 'Conditions of tumour growth. The first of the experiments is the 'matrigel' assay. Matrigel provides a matrix for the endothelial cells to grow on, and contains all the nutrients that the cells need. It is found that in the matrigel assay blood vessels didn't form, although some transient strucutres formed at early times in the experiment. The second experiment is the 'biocure' assay. In this experiment the petri dish is filled with both endothelial and fibroblast cells. The fibroblasts form a strucutal supporting network for the endothelial cells. Tubules resembling blood-vessels formed after about ten days in the biocure asssay. The process of cell differentiation is thought to be important in the growth of blood vessels. Cells can sense that they are part of a blood vessel, and change their shape to form tubules. Also it is likely that they change their chemical messaging properties, and their abilities to bind to other endothelial cells. A model is developed that describes cell differentiation, and separates cells into different classes. For simplicity the spatial distribution of cells in different classes is ignored. Using simple population dynamics, a set of coupled non-linear ODEs is developed to describe the dynamics of the system. The system is found to have two different long-time states, one corresponding to the formation of blood vessels and one where vessels did not form. The ratio of the cell proliferation rate to the cell maturity rate (the time it takes to realise that it is part of a blood vessel) is critical in determining which is the final state of the system

DNA methylation and regulatory elements during chicken germline stem cell differentiation

Funding for Open Access provided by the UMD Libraries' Open Access Publishing Fund.The production of germ cells in vitro would open important new avenues for stem biology and human medicine, but the mechanisms of germ cell differentiation are not well understood. The chicken, as a great model for embryology and development, was used in this study to help us explore its regulatory mechanisms. In this study, we reported a comprehensive genome-wide DNA methylation landscape in chicken germ cells, and transcriptomic dynamics was also presented. By uncovering DNA methylation patterns on individual genes, some genes accurately modulated by DNA methylation were found to be associated with cancers and virus infection, e.g., AKT1 and CTNNB1. Chicken-unique markers were also discovered for identifying male germ cells. Importantly, integrated epigenetic mechanisms were explored during male germ cell differentiation, which provides deep insight into the epigenetic processes associated with male germ cell differentiation and possibly improves treatment options to male infertility in animals and humans

PLLA/ZnO nanocomposites: dynamic surfaces to harness cell differentiation

This work investigates the effect of the sequential availability of ZnO nanoparticles, (nanorods of ∼40 nm) loaded within a degradable poly(lactic acid) (PLLA) matrix, in cell differentiation. The system constitutes a dynamic surface, in which nanoparticles are exposed as the polymer matrix degrades. ZnO nanoparticles were loaded into PLLA and the system was measured at different time points to characterise the time evolution of the physicochemical properties, including wettability and thermal properties. The micro and nanostructure were also investigated using AFM, SEM and TEM images. Cellular experiments with C2C12 myoblasts show that cell differentiation was significantly enhanced on ZnO nanoparticles—loaded PLLA, as the polymer degrades and the availability of nanoparticles become more apparent, whereas the release of zinc within the culture medium was negligible. Our results suggest PLLA/ZnO nanocomposites can be used as a dynamic system where nanoparticles are exposed during degradation, activating the material surface and driving cell differentiation