Impaired Spleen Formation Perturbs Morphogenesis of the Gastric Lobe of the Pancreas

Despite the extensive use of the mouse as a model for studies of pancreas development and disease, the development of the gastric pancreatic lobe has been largely overlooked. In this study we use optical projection tomography to provide a detailed three-dimensional and quantitative description of pancreatic growth dynamics in the mouse. Hereby, we describe the epithelial and mesenchymal events leading to the formation of the gastric lobe of the pancreas. We show that this structure forms by perpendicular growth from the dorsal pancreatic epithelium into a distinct lateral domain of the dorsal pancreatic mesenchyme. Our data support a role for spleen organogenesis in the establishment of this mesenchymal domain and in mice displaying perturbed spleen development, including Dh +/−, Bapx1−/− and Sox11−/−, gastric lobe development is disturbed. We further show that the expression profile of markers for multipotent progenitors is delayed in the gastric lobe as compared to the splenic and duodenal pancreatic lobes. Altogether, this study provides new information regarding the developmental dynamics underlying the formation of the gastric lobe of the pancreas and recognizes lobular heterogeneities regarding the time course of pancreatic cellular differentiation. Collectively, these data are likely to constitute important elements in future interpretations of the developing and/or diseased pancreas

Retinoic Acid Promotes the Generation of Pancreatic Endocrine Progenitor Cells and Their Further Differentiation into β-Cells

The identification of secreted factors that can selectively stimulate the generation of insulin producing β-cells from stem and/or progenitor cells represent a significant step in the development of stem cell-based β-cell replacement therapy. By elucidating the molecular mechanisms that regulate the generation of β-cells during normal pancreatic development such putative factors may be identified. In the mouse, β-cells increase markedly in numbers from embryonic day (e) 14.5 and onwards, but the extra-cellular signal(s) that promotes the selective generation of β-cells at these stages remains to be identified. Here we show that the retinoic acid (RA) synthesizing enzyme Raldh1 is expressed in developing mouse and human pancreas at stages when β-cells are generated. We also provide evidence that RA induces the generation of Ngn3+ endocrine progenitor cells and stimulates their further differentiation into β-cells by activating a program of cell differentiation that recapitulates the normal temporal program of β-cell differentiation

A framework for measuring sustainability in the Swedish food system : indicator selection and justification

Being able to assess the sustainability of food systems is central to evaluate policy implemented to remedy their sustainability problems, to monitor performance over time and to function as input to policy makers’ decisions. This report introduces a catalogue of suggested themes, sub-themes and indicators for assessing food system sustainability in Sweden. The themes, sub-themes and indicators builds on previous work that developed food system sustainability frameworks, mainly Hebinck et al. (2021) who suggests an integrated framework for food system sustainability assessment building on a comprehensive review of the literature.From a conceptual perspective, the report builds on a model developed by Mistra Food Futures researchers in 2022 - 23 (Hansson et al., 2023), where a food system sustainability framework for Sweden is suggested to take the form of a Food System Sustainability House(Fig 1). The Food System Sustainability House is developed around the following key assumptions about a sustainable food system:The overall aim of a national food system (following Hebinck et al. (2021)) is to provide healthy, safe and adequate diets for all. In addition, the food system should be just, ethical and equitable. These two aspects form the ceiling of the food system.The environmental foundations for the food system activities are viewed as afloor, or as a foundation for the system, representing restrictions on human actions and behaviors within the system. The environmental foundations are central for future continuous food security, and the food system has to rest upon a functioning ecosystem foundation. The economic system takes the role of an enabler, which makes the system work. To this end, we need companies that can produce raw material and food, and policy that can ensure, that external effects by the food system actors are taken into considerations by actors in their decision-making. This implies that the external effects are internalized. The economic indicators developed for the Food System Sustainability House for Sweden are designed to measure performance in relation to this overall function of the system. The economic system, separated between enablers for producers and consumers on the one hand side and governance on the other hand side, functions as ‘walls’ in the system, connecting the floor with the ceiling.The report now continues by introducing and motivating themes and indicators to assess food system sustainability based on the Food System Sustainability House. The themes and indicators are adapted for the Swedish food system.For each indicator, we give suggestions for official and what we call science-based targets. Official targets are targets currently reflected in official policy documents. Such are currently lacking for most of the indicators. Each indicator are also classified using the Driver (D)-Pressure (P)-State (S)-Impact (I)-Response (R) framework (Kristensen, 2004). This framework illustrate where along the cause-effect chain indicators are located. Drivers include the human activities that drivepressures (e.g. natural resource use, emissions) that lead to a change in the socioeconomic and ecological state and impacts on these systems that eventually lead to societal responses (e.g. policy responses)

Optical Projection Tomography as a quantitative 3D validation technique for MRI of labeled pancreatic islets

Rangarajan J.R., Yin T., Gilbert J., Atre A., Ribeiro R., Eriksson A., Dresselaers T., Maes F., Ahlgren U., Himmelreich U., ''Optical Projection Tomography as a quantitative 3D validation technique for MRI of labeled pancreatic islets'', European molecular imaging meeting - EMIM 2014, June 4-6, 2014, Antwerp, Belgium.status: publishe

Near infrared optical projection tomography for assessments of beta-cell mass distribution in diabetes research

By adapting OPT to include the capability of imaging in the near infrared (NIR) spectrum, we here illustrate the possibility to image larger bodies of pancreatic tissue, such as the rat pancreas, and to increase the number of channels (cell types) that may be studied in a single specimen. We further describe the implementation of a number of computational tools that provide: 1/ accurate positioning of a specimen's (in our case the pancreas) centre of mass (COM) at the axis of rotation (AR)2; 2/ improved algorithms for post-alignment tuning which prevents geometric distortions during the tomographic reconstruction2 and 3/ a protocol for intensity equalization to increase signal to noise ratios in OPT-based BCM determinations3. In addition, we describe a sample holder that minimizes the risk for unintentional movements of the specimen during image acquisition. Together, these protocols enable assessments of BCM distribution and other features, to be performed throughout the volume of intact pancreata or other organs (e.g. in studies of islet transplantation), with a resolution down to the level of individual islets of Langerhans

Improving signal detection in emission optical projection tomography via single source multi-exposure image fusion

Abstract We demonstrate a technique to improve structural data obtained from Optical Projection Tomography (OPT) using Image Fusion (IF) and contrast normalization. This enables the visualization of molecular expression patterns in biological specimens with highly variable contrast values. In the approach, termed IF-OPT, different exposures are fused by assigning weighted contrasts to each. When applied to projection images from mouse organs and digital phantoms our results demonstrate the capability of IF-OPT to reveal high and low signal intensity details in challenging specimens. We further provide measurements to highlight the benefits of the new algorithm in comparison to other similar methods