No abstract

The dynamics of dissolved oxygen (DO) and shear stress in the vasculature microenvironment play a major role in determining the fate of stem cells in adults and during early embryonic development. In this study, we present a microbioreactor (MBR) that provides independent control over oxygen tension and shear stress in cultures of stem and progenitor cell types. We first describe the design principles and use a model-driven approach for the optimization of the MBR geometry and operating conditions prior to its fabrication and assembly. We then demonstrate the utilization of the MBR for culturing adult human endothelial progenitors, human umbilical vein endothelial cells, and human embryonic stem cell-derived smooth muscle cells under different DO and shear stress levels.

(Abstracted from Nat Cell Biol 2021;23:314–321) Despite it being current practice in vitro fertilization (IVF) protocols to exclude aneuploid embryos diagnosed through preimplantation genetic testing (PGT-A), it remains controversial whether or not this improves IVF outcomes. Both IVF pregnancies and spontaneous pregnancies demonstrate similar levels of mosaicism (12% vs 6.3%).

The fat mass and obesity-associated gene ( FTO) codes for a DNA/RNA demethylase. Pathological variants in this gene are rare, with only three reports in the literature, all with mutations in the catalytic domain. We report the first biallelic human variant in fat mass and obesity-associated gene (c.287G>C, p.Arg96Pro/R96P) outside the catalytic site, causing numerous abnormalities across multiple organ systems, affecting respiratory, cardiovascular, and neurological function. Biochemical assays of cells with the patient’s variant were performed to further quantify the effect of the variant on function. Loss-of-function resulting from the patient’s R96P missense variant was demonstrated with in vitro biochemical characterization of demethylase activity, resulting in a 90% reduction in function of the fat mass and obesity-associated protein compared to wild-type. Our findings demonstrate a novel fat mass and obesity-associated gene non-catalytic site variant with a unique patient phenotype of bilateral multifocal epilepsy and multisystem congenital anomalies.