ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency Investigators showed that the estrogen-related nuclear receptors (ERRα and ERRγ) and their partnered co-factors PGC-1α and PGC-1β are transiently induced at an early stage, resulting in a burst of oxidative phosphorylation (OXPHOS) activity. Upregulation of ERRα or ERRγ is required for the OXPHOS burst in both human and mouse cells, respectively, as well as induced pluripotent stem cell generation itself. [Cell Stem Cell] Abstract | Graphical Abstract Pontin Functions as an Essential Coactivator for OCT4-Dependent lincRNA Expression in Mouse Embryonic Stem Cells The authors found that pontin chromatin remodeling factor plays an essential role as a coactivator for OCT4 for maintenance of pluripotency in mouse embryonic stem (ES) cells. Genome-wide analyses revealed that pontin and OCT4 share a substantial set of target genes involved in ES cell maintenance. [Nat Commun] Abstract | Full Article A Cohesin–Oct4 Complex Mediates Sox Enhancers to Prime an Early Embryonic Lineage Scientists reported a chromatin-remodeling mechanism and enhancer function that mediate cell fate switching. Oct4 alters the higher-order chromatin structure at both Sox-2 and Sox-17 loci. Oct4 titrates out cohesin and switches the Sox-17 enhancer from a locked to an active state. [Nat Commun] Abstract Heightened Potency of Human Pluripotent Stem Cell Lines Created by Transient BMP4 Exposure Investigators report the acquisition of a unique stem cell phenotype by both human embryonic stem cells and induced pluripotent stem cells (PSCs) in response to transient exposure to bone morphogenetic protein 4 (BMP4) plus inhibitors of ACTIVIN signaling and FGF2, followed by trypsin dissociation and recovery of colonies capable of growing on a gelatin substratum in standard medium for human PSCs at low but not high FGF2 concentrations. [Proc Natl Acad Sci USA] Abstract | Full Article A Novel Autoregulatory Loop between the Gcn2-Atf4 Pathway and L-Proline Metabolism Controls Stem Cell Identity Scientists demonstrated that embryonic stem cell behavior relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response pathway that in turn regulates L-Pro biosynthesis. [Cell Death Differ] Full Article Molecular Signature of Erythroblast Enucleation in Human Embryonic Stem Cells To investigate erythroblast enucleation, researchers studied the erythroid differentiation of human embryonic stem cells (hESCs). They demonstrated that terminal erythroid differentiation from hESCs is directly dependent on the age of the embryoid bodies. [Stem Cells] Abstract piggyBac Insertional Mutagenesis Screen Identifies a Role for Nuclear RHOA in Human Embryonic Stem Cell Differentiation Scientists present a piggyBac transposon gain of function screen in human embryonic stem cells that identified DENND2C, which genetically cooperates with NANOG to maintain self-renewal in the presence of retinoic acid. They showed that DENND2C negatively regulates RHOA activity, which cooperates with NANOG to block differentiation. [Stem Cell Reports] Full Article Elimination of Tumorigenic Human Pluripotent Stem Cells by a Recombinant Lectin-Toxin Fusion Protein Researchers developed a recombinant lectin-toxin fusion protein of rBC2LCN with a catalytic domain of Pseudomonas aeruginosa exotoxin A, termed rBC2LCN-PE23. rBC2LCN-PE23 bound to human pluripotent stem cells, followed by its internalization, allowing intracellular delivery of a cargo of cytotoxic protein. The addition of rBC2LCN-PE23 to the culture medium was sufficient to completely eliminate human pluripotent stem cells. [Stem Cell Reports] Full Article | Graphical Abstract |