Pioneer Transcription Factors Target Partial DNA Motifs on Nucleosomes to Initiate Reprogramming The authors compared the nucleosome and chromatin targeting activities of Oct4, Sox2, Klf4, and c-Myc, which together reprogram somatic cells to pluripotency. Purified Oct4, Sox2, and Klf4 proteins can bind nucleosomes in vitro, and in vivo they preferentially target silent sites enriched for nucleosomes. [Cell] Abstract | Graphical Abstract | Press Release Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation Investigators demonstrated discrete and opposing roles for the long noncoding RNA (lncRNA) transcript Haunt and its genomic locus in regulating the HOXA gene cluster during embryonic stem cell differentiation. [Cell Stem Cell] Abstract | Graphical Abstract Myc and SAGA Rewire an Alternative Splicing Network during Early Somatic Cell Reprogramming Scientists performed a functional RNAi screen to identify the earliest epigenetic regulators required for reprogramming. They identified components of the SAGA histone acetyltransferase complex, in particular Gcn5, as critical regulators of reprogramming initiation. [Genes Dev] Abstract Foxp1-Mediated Programming of Limb-Innervating Motor Neurons from Mouse and Human Embryonic Stem Cells Researchers demonstrated that limb-innervating lateral motor column spinal motor neurons can be efficiently generated from mouse and human embryonic stem cells through manipulation of the transcription factor Foxp1. [Nat Commun] Full Article Functional and Mechanistic Studies of XPC DNA-Repair Complex as Transcriptional Coactivator in Embryonic Stem Cells The authors provide novel insights into transcriptional regulation of the stem cell state by characterizing interactions between key transcription factors SOX2 and OCT4, and a multifunctional, stem cell coactivator—the xeroderma pigmentosum, complementation group C (XPC) DNA repair complex—to control pluripotency gene-expression networks. [Proc Natl Acad Sci USA] Abstract Mitofusins Deficiency Elicits Mitochondrial Metabolic Reprogramming to Pluripotency Researchers showed that depleting p53 and p21, which are barriers to reprogramming, yields a high reprogramming efficiency. Deletion of these factors results in a distinct mitochondrial background with low expression of oxidative phosphorylation subunits and mitochondrial fusion proteins, including mitofusin 1 and 2. [Cell Death Differ] Abstract Defining Minimum Essential Factors to Derive Highly Pure Human Endothelial Cells from iPS/ES Cells in an Animal Substance-Free System Investigators developed a way to differentiate human induced pluripotent stem (iPS) cells and embryonic stem (ES) cells to highly pure endothelial cells in five days. The chemically defined system is robust, easy to perform, and free of animal substances. [Sci Rep] Full Article Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions Scientists found that culture conditions affected pluripotent and metabolic features of porcine pluripotent induced stem cells (iPSCs). Using defined human embryonic stem cell (hESC) and mouse embryonic stem cell (mESC) culture conditions, they generated two types of porcine iPSCs, one of which was morphologically similar to hESCs, the other resembled mESCs. [PLoS One] Full Article |