Single-Cell Genome-Wide Bisulfite Sequencing for Assessing Epigenetic Heterogeneity Researchers report a single-cell bisulfite sequencing method that can be used to accurately measure DNA methylation at up to 48.4% of CpG sites. Embryonic stem cells grown in serum or in 2i medium displayed epigenetic heterogeneity, with ‘2i-like’ cells present in serum culture. [Nat Methods] Abstract | Press Release Role of Astroglia in Down’s Syndrome Revealed by Patient-Derived Human-Induced Pluripotent Stem Cells Scientists used induced pluripotent stem cells derived from Down’s syndrome (DS) patients to identify a role for astrocytes in DS pathogenesis. [Nat Commun] Full Article | Press Release Embryonic Stem Cell-Specific MicroRNAs Contribute to Pluripotency by Inhibiting Regulators of Multiple Differentiation Pathways To elucidate the transcription regulatory networks immediately downstream of embryonic microRNAs (miRNAs) , investigators extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors and miRNAs from genome-wide expression states. [Nucleic Acids Res] Full Article ADP-Ribosyltransferases Parp1 and Parp7 Safeguard Pluripotency of ES Cells Researchers find that the ADP-ribosyltransferases Parp1 and Parp7 play a critical role in safeguarding this state by occupying key pluripotency genes, notably Nanog, Pou5f1, Sox2, Stella, Tet1 and Zfp42, thereby protecting them from progressive epigenetic repression. [Nucleic Acids Res] Full Article Spider Silk for Xeno-Free Long-Term Self-Renewal and Differentiation of Human Pluripotent Stem Cells Scientists mimic spider silk for the design of chemically defined two-dimensional (2D) and 3D matrices for cell culture. The silk matrices do not only allow xeno-free long-term expansion of human pluripotent stem cells but also differentiation in both 2D and 3D. [Biomaterials] Abstract Functional and Molecular Defects of hiPSC-Derived Neurons from Patients with ATM Deficiency To investigate the mechanisms of neurodegeneration, researchers reprogrammed fibroblasts from ataxia telangiectasia mutated (ATM)-null ataxia-telangiectasia patients and normal controls to pluripotency (human-induced pluripotent stem cells [hiPSCs]), and derived from these neural precursor cells able to terminally differentiate into post-mitotic neurons positive to >90% for β-tubulin III+/microtubule-associated protein 2+. [Cell Death Dis] Full Article Induced Pluripotent Stem Cells from Familial Alzheimer’s Disease Patients Differentiate into Mature Neurons with Amyloidogenic Properties Scientists describe the generation of virus-free human induced pluripotent stem cells derived from fibroblasts of patients harboring the familial Alzheimer’s disease presenilin 1 mutation A246E and fibroblasts from healthy age-matched controls using non-integrating episomal vectors. [Stem Cells Dev] Abstract Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart Syndrome Scientists investigated the altered control of transcriptional and epigenetic programs that may affect the development of hypoplastic left heart syndrome by using disease-specific induced pluripotent stem cells. [PLoS One] Full Article Removal of Reprogramming Transgenes Improves the Tissue Reconstitution Potential of Keratinocytes Generated from Human Induced Pluripotent Stem Cells The authors generated human induced pluripotent stem cell (hiPSC) lines from normal human dermal fibroblasts with piggyBac transposon bearing reprogramming transgenes followed by removal of the transposon by the transposase. Under this condition, they compared the phenotypes of transgene-residual and -free hiPSCs of the same genetic background. [Stem Cells Transl Med] Abstract Genome-Wide Functional Analysis Reveals Factors Needed at the Transition Steps of Induced Reprogramming Investigators used a genome-wide RNAi screen and performed integrated transcriptome analysis to identify key genes and cellular events required at the transition steps in reprogramming [Cell Rep] Full Article | Graphical Abstract |