Proteomic and Genomic Approaches Reveal Critical Functions of H3K9 Methylation and Heterochromatin Protein-1γ in Reprogramming to Pluripotency Scientists found that induced pluripotent stem cells, compared with both the starting fibroblasts and a late reprogramming intermediate, are enriched for histone modifications associated with active chromatin, and depleted for marks of transcriptional elongation and a subset of repressive modifications including H3K9me2/me3. [Nat Cell Biol] Abstract Embryonic Stem Cell-Derived CD166+ Precursors Develop into Fully Functional Sinoatrial-Like Cells Investigators explored the possibility to use CD166 expression for isolating sinoatrial node (SAN) progenitors from differentiating embryonic stem cells. They demonstrated for the first time the isolation of a non-teratogenic population of cardiac precursors able to mature and form a fully functional SAN-like tissue. [Circ Res] Abstract USF1 and hSET1A Mediated Epigenetic Modifications Regulate Lineage Differentiation and HoxB4 Transcription The authors report that the recruitment of the hSET1A histone H3K4 methyltransferase complex by transcription factor USF1 is required for mesoderm specification and lineage differentiation. In undifferentiated embryonic stem cells, USF1 maintains hematopoietic stem/progenitor cell associated bivalent chromatin domains and differentiation potential. [PLoS Genet] Full Article TRF1 Is a Stem Cell Marker and Is Essential for the Generation of Induced Pluripotent Stem Cells Investigators generated a reporter mouse carrying a knock-in eGFP-TRF1 fusion allele to study the role of TRF1 in stem cell biology and tissue homeostasis. They showed that TRF1 is necessary for both induction and maintenance of pluripotency, and that TRF1 is a direct transcriptional target of Oct3/4. [Nat Commun] Abstract | Press Release Zscan4 Restores the Developmental Potency of Embryonic Stem Cells Researchers showed that increasing the frequency of Zscan4 activation in mouse embryonic stem cells restores and maintains their developmental potency in long-term cell culture. [Nat Commun] Abstract Kinetics and Epigenetics of Retroviral Silencing in Mouse Embryonic Stem Cells Defined by Deletion of the D4Z4 Element Using FLP recombinase to induce deletion of 3'D4Z4 from the provirus in embryonic stem cell clones, researchers established retroviral silencing at many but not all integration sites. This finding shows that 3'D4Z4 does not target retrovirus integration into favorable epigenomic domains but rather protects the transgene from silencing. [Mol Ther] Full Article Developing High-Fidelity Hepatotoxicity Models from Pluripotent Stem Cells Pluripotent stem cells were differentiated to hepatocytes before being replated onto a synthetic surface. The approach yielded metabolically active hepatocyte populations that displayed stable function for more than two weeks in vitro. The authors report that pluripotent stem cell-derived hepatocytes will model toxicity predictably and in a manner comparable to current gold standard assays, representing a major advance in the field. [Stem Cells Transl Med] Abstract | Press Release Totipotent Embryonic Stem Cells Arise in Ground-State Culture Conditions Embryonic stem cells (ESCs) maintained with inhibitors of MEK and GSK3 (2i) are thought to represent an embryonically restricted ground state. However, investigators observed heterogeneous expression of the extraembryonic endoderm marker Hex in 2i-cultured embryos, suggesting that 2i blocked development prior to epiblast commitment. Similarly, 2i ESC cultures were heterogeneous and contained a Hex-positive fraction primed to differentiate into trophoblast and extraembryonic endoderm. [Cell Rep] Abstract | Full Article | Graphical Abstract | Press Release |