One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering Investigators demonstrated that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes (Tet1, 2, 3, Sry, Uty - 8 alleles) in mouse embryonic stem cells with high efficiency. [Cell] Abstract | Graphical Abstract | Press Release Directed Differentiation and Functional Maturation of Cortical Interneurons from Human Embryonic Stem Cells Investigators demonstrated the highly efficient derivation of human cortical interneurons in an NKX2.1::GFP human embryonic stem cell reporter line. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release Functional Maturation of hPSC-Derived Forebrain Interneurons Requires an Extended Timeline and Mimics Human Neural Development Researchers report the directed differentiation of human pluripotent stem cells (hPSCs) into medial ganglionic eminence (MGE)-like progenitors and their maturation into forebrain type interneurons. Both in vitro and posttransplantation into the rodent cortex, the MGE-like cells develop into GABAergic interneuron subtypes with mature physiological properties along a prolonged intrinsic timeline of up to seven months, mimicking endogenous human neural development. [Cell Stem Cell] Abstract | Graphical Abstract | Press Release Derivation of Extraembryonic Endoderm Stem (XEN) Cells from Mouse Embryos and Embryonic Stem Cells At the time of implantation in the maternal uterus, the mouse blastocyst possesses an inner cell mass comprising two lineages: epiblast and primitive endoderm. Representative stem cells derived from these two cell lineages can be expanded and maintained indefinitely in vitro as either embryonic stem or XEN cells, respectively. Researchers described protocols that can be used to establish XEN cell lines. [Nat Protoc] Abstract Engineering Bone Tissue Substitutes from Human Induced Pluripotent Stem Cells Researchers induced three human-induced pluripotent stem cell (hiPSC) lines with different tissue and reprogramming backgrounds into the mesenchymal lineages and used a combination of differentiation assays, surface antigen profiling, and global gene expression analysis to identify the lines exhibiting strong osteogenic differentiation potential. They then engineered functional bone substitutes by culturing hiPSC-derived mesenchymal progenitors on osteoconductive scaffolds in perfusion bioreactors and confirmed their phenotype stability in a subcutaneous implantation model for 12 weeks. [Proc Natl Acad Sci USA] Abstract | Press Release Hes1 Desynchronizes Differentiation of Pluripotent Cells by Modulating STAT3 Activity Robust development of the early embryo may benefit from mechanisms that ensure that not all pluripotent cells differentiate at exactly the same time: such mechanisms would build flexibility into the process of lineage allocation. Researchers used a clonal commitment assay to confirm that pluripotent cells commit to differentiate asynchronously even under uniform differentiation conditions. [Stem Cells] Abstract | Full Article Tissue-Engineered Cardiac Patch for Advanced Functional Maturation of Human ESC-Derived Cardiomyocytes Scientists investigated the effects of 3-dimensional tissue-engineered culture environment and cardiomyocyte purity on structural and functional maturation of human embryonic stem cell (ESC)-derived cardiomyocytes. [Biomaterials] Abstract | Press Release SMRT Compounds Abrogate Cellular Phenotypes of Ataxia Telangiectasia in Neural Derivatives of Patient-Specific hiPSCs Investigators presented a model of human ataxia telangiectasia using induced pluripotent stem cells, and showed that small molecule read-through compounds, designed to induce read-through of mRNA around premature termination codons, restore ATM activity and improve the response to DNA damage. [Nat Commun] Abstract | Press Release Repression of Global Protein Synthesis by Eif1a-Like Genes That Are Expressed Specifically in the Two-Cell Embryos and the Transient Zscan4-Positive State of Embryonic Stem Cells Researchers reported that the nascent protein synthesis is globally repressed in the Zscan4-positive state of embryonic stem cells, which is mediated by the transient expression of newly identified eukaryotic translation initiation factor 1A (Eif1a)-like genes. [DNA Res] Full Article Generation of Integration-Free and Region-Specific Neural Progenitors from Primate Fibroblasts Postnatal and adult human and monkey fibroblasts were infected with Sendai virus containing the Yamanaka factors for 24 hours, then they were cultured in a chemically defined medium containing leukemia inhibitory factor, transforming growth factor-β inhibitor SB431542, and glycogen synthase kinase-3β inhibitor CHIR99021 at 39°C for inactivation of the virus. Induced neural progenitor (iNP) colonies appeared as early as day 13 and can be expanded for >20 passages. Following transplantation into the forebrain, the iNP-derived cells retained the hindbrain identity. [Cell Reports] Abstract | Graphical Abstract | Press Release |