Human Disease Modeling Reveals Integrated Transcriptional and Epigenetic Mechanisms of NOTCH1 Haploinsufficiency Investigators utilized human induced pluripotent stem cell-derived endothelial cells to show that heterozygous nonsense mutations in NOTCH1 that cause aortic valve calcification disrupt the epigenetic architecture, resulting in derepression of latent pro-osteogenic and -inflammatory gene networks. [Cell] Abstract | Graphical Abstract | Press Release Lymphoid Regeneration from Gene-Corrected SCID-X1 Subject-Derived iPSCs X-linked severe combined immunodeficiency (SCID-X1) pathogenesis is due to mutations in the gene encoding the interleukin-2 receptor gamma chain, leading to a lack of functional lymphocytes. Researchers utilized induced pluripotent stem cell (iPSC) technology and genome editing mediated by TALENs to generate isogenic subject-specific mutant and gene-corrected iPSC lines. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release | Video Smg6/Est1 Licenses Embryonic Stem Cell Differentiation via Nonsense-Mediated mRNA Decay Scientists generated knockout mice lacking Smg6/Est1, a key nuclease in nonsense-mediated mRNA decay (NMD) and a telomerase cofactor. While the complete loss of Smg6 causes mouse lethality at the blastocyst stage, inducible deletion of Smg6 is compatible with embryonic stem cell proliferation despite the absence of telomere maintenance and functional NMD. [EMBO J] Full Article | Graphical Abstract Cellular Reprogramming Allows Generation of Autologous Hematopoietic Progenitors from AML Patients that Are Devoid of Patient-Specific Genomic Aberrations Skin fibroblasts were obtained from acute myeloid leukemia (AML) patients whose leukemic cells possessed a distinct, leukemia-associated aberration, and used to create AML patient-specific induced pluripotent stem cells. [Stem Cells] Abstract New Protocol to Optimize iPS Cells for Genome Analysis of Fibrodysplasia Ossificans Progressiva Investigators identified MMP1 and PAI1 as genes responsible for accelerating the chondrogenesis of fibrodysplasia ossificans progressiva-induced mesenchymal stromal cells. [Stem Cells] Abstract Nr0b1 Is a Negative Regulator of Zscan4c in Mouse Embryonic Stem Cells Scientists generated inducible knockout embryonic stem cells for nuclear receptor subfamily 0, group B, member 1 (Nr0b1) using the Cre-loxP system and analyzed its precise function. [Sci Rep] Full Article Dual Optical Recordings for Action Potentials and Calcium Handling in Induced Pluripotent Stem Cell Models of Cardiac Arrhythmias Using Genetically Encoded Fluorescent Indicators Investigators optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. [Stem Cells Transl Med] Abstract Pluripotent Cell Models of Fanconi Anemia Identify the Early Pathological Defect in Human Hemoangiogenic Progenitors Scientists established induced pluripotent stem cells (iPSCs) from fibroblasts of six patients with Fanconi anemia (FA) and FANCA mutations. An improved reprogramming method yielded iPSC-like colonies from all patients, and iPSC clones were propagated from two patients. Quantitative evaluation of the differentiation ability demonstrated that the differentiation propensity toward the hematopoietic and endothelial lineages is already defective in early hemoangiogenic progenitors. [Stem Cells Transl Med] Abstract Resveratrol Ameliorates the Maturation Process of β-Cell-Like Cells Obtained from an Optimized Differentiation Protocol of Human Embryonic Stem Cells Investigators optimized an efficient differentiation protocol that mimics in vivo pancreatic organogenesis and investigated whether resveratrol may improve the final maturation step to obtain functional insulin-secreting cells. [PLoS One] Full Article Inducible and Reversible Lentiviral and Recombination Mediated Cassette Exchange (RMCE) Systems for Controlling Gene Expression Researchers developed broadly applicable platforms for reliable, tightly controlled and reversible Dox-inducible systems for lentiviral mediated generation of cell lines or FLP RMCE into the collagen 1a1 locus in mouse embryonic stem cells. [PLoS One] Full Article |