Exit from Pluripotency Is Gated by Intracellular Redistribution of the bHLH Transcription Factor Tfe3 Factors that sustain self-renewal of mouse embryonic stem cells (ESCs) are well described. In contrast, the machinery regulating exit from pluripotency is ill defined. In a large-scale small interfering RNA screen, researchers found that knockdown of the tumor suppressors Folliculin (Flcn) and Tsc2 prevent ESC commitment. [Cell] Abstract | Graphical Abstract Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes Master transcription factors Oct4, Sox2, and Nanog bind enhancer elements and recruit Mediator to activate much of the gene expression program of pluripotent embryonic stem cells (ESCs). Scientists report that the ESC master transcription factors form unusual enhancer domains at most genes that control the pluripotent state. [Cell] Abstract | Graphical Abstract Generation of Oligodendroglial Cells by Direct Lineage Conversion Investigators report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. [Nat Biotechnol] Abstract | Press Release A Simple Tool to Improve Pluripotent Stem Cell Differentiation Researchers described a method to help overcome restrictions on the differentiation propensities of human pluripotent stem cells. Culturing pluripotent stem cells in dimethylsulfoxide activates the retinoblastoma protein, increases the proportion of cells in the early G1 phase of the cell cycle and, in more than 25 embryonic and induced pluripotent stem cell lines, improves directed differentiation into multiple lineages. [Nat Methods] Abstract SK4 Ca2+ Activated K+ Channel Is a Critical Player in Cardiac Pacemaker Derived from Human Embryonic Stem Cells Investigators used human embryonic stem cell-derived cardiomyocytes to study their autonomous beating mechanisms. [Proc Natl Acad Sci USA] Abstract Transcription Factors Interfering with Dedifferentiation Induce Cell Type-Specific Transcriptional Profiles Researchers showed that the transcription factors (TFs) capable of inducing cell type-specific transcriptional profiles prevent the dedifferentiation induced by TFs for pluripotency. Of the large number of TFs expressed in a neural-lineage cell line, they identified a subset of TFs that, when overexpressed, strongly interfered with the dedifferentiation triggered by the procedure to generate induced pluripotent stem cells. [Proc Natl Acad Sci USA] Full Article The Histone Demethylase Jmjd3 Sequentially Associates with the Transcription Factors Tbx3 and Eomes to Drive Endoderm Differentiation Scientists showed that T-box proteins team up with chromatin modifying enzymes to drive the expression of the key lineage regulator, Eomes during endodermal differentiation of embryonic stem cells. [EMBO J] Abstract Rigid Microenvironments Promote Cardiac Differentiation of Mouse and Human Embryonic Stem Cells Researchers examined the role of matrix rigidity on cardiac differentiation using mouse and human embryonic stem cells. [Sci Technol Adv Mater] Full Article | Press Release A Simple and Scalable Process for the Differentiation of Retinal Pigment Epithelium from Human Pluripotent Stem Cells Most protocols developed to date for deriving retinal pigment epithelial (RPE) cells from human pluripotent stem cells (hPSCs) involve time- and labor-consuming manual steps, which hinder their use in biomedical applications requiring large amounts of differentiated cells. The authors describe a simple and scalable protocol for the generation of RPE cells from hPSCs that is less labor-intensive. [Stem Cells Transl Med] Abstract | Press Release Modeling Neural Crest Induction, Melanocyte Specification, and Disease-Related Pigmentation Defects in hESCs and Patient-Specific iPSCs Pluripotent stem cell (PSC) technology offers a promising approach for studying human melanocyte development and disease. Researchers report that timed exposure to activators of WNT, BMP, and EDN3 signaling triggers the sequential induction of neural crest and melanocyte precursor fates under dual-SMAD-inhibition conditions. [Cell Rep] Abstract | Graphical Abstract |