SCL/TAL1 cooperates with Polycomb RYBP-PRC1 to suppress alternative lineages in blood-fated cells

During development, it is unclear if lineage-fated cells derive from multilineage-primed progenitors and whether active mechanisms operate to restrict cell fate. Here we investigate how mesoderm specifies into blood-fated cells. We document temporally restricted co-expression of blood (Scl/Tal1), cardiac (Mesp1) and paraxial (Tbx6) lineage-affiliated transcription factors in single cells, at the onset of blood specification, supporting the existence of common progenitors. At the same time-restricted stage, absence of SCL results in expansion of cardiac/paraxial cell populations and increased cardiac/paraxial gene expression, suggesting active suppression of alternative fates. Indeed, SCL normally activates expression of co-repressor ETO2 and Polycomb-PRC1 subunits (RYBP, PCGF5) and maintains levels of Polycomb-associated histone marks (H2AK119ub/H3K27me3). Genome-wide analyses reveal ETO2 and RYBP co-occupy most SCL target genes, including cardiac/paraxial loci. Reduction of Eto2 or Rybp expression mimics Scl-null cardiac phenotype. Therefore, SCL-mediated transcriptional repression prevents mis-specification of blood-fated cells, establishing active repression as central to fate determination processes

DLR Simulations of the First AIAA Sonic Boom Prediction Workshop Cases

The prediction of the sonic boom signature plays an important role in the development of a supersonic transport aircraft. In this paper geometries and grids provided by the First AIAA Sonic Boom Prediction Workshop are used to develop a best practice for predicting near field pressure signatures using the DLR TAU code. The configurations include a low-boom body of revolution, a 69$^{\circ}$ delta-wing body, and a full aircraft configuration with a V-tail and flow-through nacelles. Results for the simulations on the workshop-provided tetrahedral and mixed-element grids are presented. The influence using several spatial discretization schemes is analyzed. Available experimental and numerical results from the workshop are used to assess the solutions. Compared to the solutions by the other participants, the TAU solutions appear to be less dissipative on the grids provided by the workshop and have slight overshoots at shocks and expansions. In addition to the provided grids, mixed-element grids with differing resolution setups and topologies are generated to assess the influence of near field and mid-field grid resolution on the numerical solutions. It is shown that the solutions on the self-generated grids are similar to the solutions by the other participants and improve the agreement with experimental data compared to the solutions on the provided grids