87 research outputs found
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence
Scl/Tal1 confers hemogenic competence and prevents ectopic cardiomyogenesis in embryonic endothelium by unknown mechanisms. We discovered that Scl binds to hematopoietic and cardiac enhancers that become epigenetically primed in multipotent cardiovascular mesoderm, to regulate the divergence of hematopoietic and cardiac lineages. Scl does not act as a pioneer factor but rather exploits a pre-established epigenetic landscape. As the blood lineage emerges, Scl binding and active epigenetic modifications are sustained in hematopoietic enhancers, whereas cardiac enhancers are decommissioned by removal of active epigenetic marks. Our data suggest that, rather than recruiting corepressors to enhancers, Scl prevents ectopic cardiogenesis by occupying enhancers that cardiac factors, such as Gata4 and Hand1, use for gene activation. Although hematopoietic Gata factors bind with Scl to both activated and repressed genes, they are dispensable for cardiac repression, but necessary for activating genes that enable hematopoietic stem/progenitor cell development. These results suggest that a unique subset of enhancers in lineage-specific genes that are accessible for regulators of opposing fates during the time of the fate decision provide a platform where the divergence of mutually exclusive fates is orchestrated
Diverse effect of BMP-2 homodimer on mesenchymal progenitors of different origin
Bone morphogenetic protein-2 (BMP-2), is a potential factor to enhance osseointegration of dental implants. However, the appropriate cellular system to investigate the osteogenic effect of BMP-2 in vitro in a standardized manner still needs to be defined. The aim of this study was to examine the effect of BMP-2 on the cell proliferation and osteogenic differentiation of human osteogenic progenitors of various origins: dental pulp stem cells (DPSC), human osteosarcoma cell line (Saos-2) and human embryonic palatal mesenchymal cell line (HEPM). For induction of osteogenic differentiation, cell culture medium was supplemented with BMP-2 homodimer alone or in combination with conventionally used differentiation inducing agents. Differentiation was monitored for 6-18 days. To assess differentiation, proliferation rate, alkaline phosphatase activity, calcium deposition and the expression level of osteogenic differentiation marker genes (Runx2, BMP-2) were measured. BMP-2 inhibited cell proliferation in a concentration and time-dependent manner. In a concentration which caused maximal cell proliferation, BMP-2 did not induce osteogenic differentiation in any of the tested systems. However, it had a synergistic effect with the osteoinductive medium in both DPSC and Saos-2, but not in HEPM cells. We also found that the differentiation process was faster in Saos-2 than in DPSCs. Osteogenic differentiation could not be induced in the osteoblast progenitor HEPM cells. Our data suggest that in a concentration that inhibits proliferation the differentiation inducing effect of BMP-2 is evident only in the presence of permissive osteoinductive components. beta-glycerophosphate, was identified interacting with BMP-2 in a synergistic manner
Vacuum Chamber Design for RATEX-J Radiation Testing
Calibration of particle detectors for space plasma sensors is an essential part of instrument development process. The Jovian plasma Dynamics and Composition analyzer (JDC) is one of the two instruments built by the Swedish Institute of Space Physics, for the Europen Space Agencyâs JUICE (JUpiter ICy moon Explorer) mission. RATEX-J (RAdiation Test EXperiment for JUICE) is a project aiming to perform radiation tests to characterize the sensors and test the anti-coincidence system of JDC. Particle detectors operate in high quality vacuum only, hence a vacuum system is imperative for these tests.This report focuses on the vacuum system designed for the RATEX-J experiment. After the requirements were established, a DN 160 ISO-K four way cross was selected as a vacuum tank, then each wall was designed to accommodate the needed appliances and connectors. Finally a support structure was built to meet mobility and stability requirements.The system performance during the ïŹrst radiation campaign was satisfactory. After concluding the test results, a few alterations were requested to adapt the system for the next test session.Finally a larger vacuum system and a motorized manipulator design is discussed, which are planned for radiation test of the complete JDC instrument
Vacuum Chamber Design for RATEX-J Radiation Testing
Calibration of particle detectors for space plasma sensors is an essential part of instrument development process. The Jovian plasma Dynamics and Composition analyzer (JDC) is one of the two instruments built by the Swedish Institute of Space Physics, for the Europen Space Agencyâs JUICE (JUpiter ICy moon Explorer) mission. RATEX-J (RAdiation Test EXperiment for JUICE) is a project aiming to perform radiation tests to characterize the sensors and test the anti-coincidence system of JDC. Particle detectors operate in high quality vacuum only, hence a vacuum system is imperative for these tests.This report focuses on the vacuum system designed for the RATEX-J experiment. After the requirements were established, a DN 160 ISO-K four way cross was selected as a vacuum tank, then each wall was designed to accommodate the needed appliances and connectors. Finally a support structure was built to meet mobility and stability requirements.The system performance during the ïŹrst radiation campaign was satisfactory. After concluding the test results, a few alterations were requested to adapt the system for the next test session.Finally a larger vacuum system and a motorized manipulator design is discussed, which are planned for radiation test of the complete JDC instrument
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