Short Telomeres in ESCs Lead to Unstable Differentiation

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Highlights? ESCs with short telomeres do not stably differentiate and can resume proliferation ? Critically short telomeres impair Nanog regulation during ESC differentiation ? Short telomeres elicit genome-wide DNA hypomethylation and altered H3K27me3 levels ? Impaired DNA methylation and differentiation are rescued by Dnmt3b or telomere elongation     

RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection

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Highlights? RIF1 is essential for 53BP1-dependent CSR and fusion of dysfunctional telomeres ? BRCA1 antagonizes RIF1 in S phase to prevent error-prone repair by toxic NHEJ ? N-terminal phospho-SQ/TQ domain of 53BP1 interacts with and recruits RIF1 to DSBs ? RIF1 and 53BP1 promote NHEJ in G1 by blocking 5′ end resection of DSBs     

Stage-Specific Roles for Tet1 and Tet2 in DNA Demethylation in Primordial Germ Cells

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Highlights? PGCs differentiated from ESCs undergo genome-wide DNA demethylation ? Tet1 and Tet2 do not regulate genome-wide DNA demethylation in PGCs ? Tet1 and Tet2 regulate locus-specific demethylation in PGCs     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

Development and Regeneration of Sox2+ Endoderm Progenitors Are Regulated by a HDAC1/2-Bmp4/Rb1 Regulatory Pathway

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Highlights? Hdac1/2 regulate development of Sox2+ endoderm progenitors ? Bmp4, Rb1, p21, and p16 are direct targets of Hdac1/2 in lung endoderm ? Increased Bmp4 suppresses Sox2 expression in lung endoderm ? Hdac1/2 are required for lung secretory epithelial regeneration     

Generation of Rejuvenated Antigen-Specific T Cells by Reprogramming to Pluripotency and Redifferentiation

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Highlights? Reprogramming of antigen-specific T cells to generate iPSCs (T-iPSCs) ? Redifferentiation of CD8⁺ T cells, with original antigen specificity, from T-iPSCs ? Newly differentiated T cells show high proliferation and elongated telomeres ? T cell antigen-specific cytotoxicity is maintained     

LRP6 Enhances Glucose Metabolism by Promoting TCF7L2-Dependent Insulin Receptor Expression and IGF Receptor Stabilization in Humans

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Highlights? Nondiabetic LRP6 mutation carriers are hyperinsulinemic and insulin resistant ? IR expression is reduced in skeletal muscles of the LRP6 mutation carriers ? Wnt/LRP6 regulate the insulin receptor and IGFR expression ? The LRP6 mutation reduces TCF7L2-dependent IR expression and enhances mTOR activity     

Inhibition of Leptin Regulation of Parasympathetic Signaling as a Cause of Extreme Body Weight-Associated Asthma

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Highlights? Leptin regulates airway diameter, independently of body weight and inflammation ? Leptin uses the parasympathetic tone to regulate airway diameter ? Modulating the parasympathetic tone can correct bronchoconstriction in obese mice     

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

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Highlights? c-Src phosphorylates syndecan-4 in response to extracellular stimuli ? Syndecan-4 phosphorylation and engagement regulate Arf6 activity ? Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ? Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration     

Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo

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Highlights? RNA-seq, RNA Capture-Seq of SVZ-NSCs reveals unannotated lncRNAs and splice variants ? lncRNA loci have dynamic chromatin signatures, including bivalency in SVZ-NSCs ? Online resource facilitates discovery of lncRNAs involved in adult neurogenesis ? lncRNAs can regulate glial-neuronal lineage specification of SVZ-NSCs     

Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development

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Highlights? Wnt2 is required for atrial and inflow tract morphogenesis ? Wnt2 regulates expansion of secondary heart field progenitors ? Defects in Wnt2^?/? mutants can be rescued using Wnt signaling agonists ? Wnt2 cooperates with Gata6 to regulate cardiac inflow tract development     

p38 MAPK controls prothrombin expression by regulated RNA 3' end processing

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Highlights? External signals regulate 3′ end mRNA processing through p38 MAPK activation ? The mechanism is controlled by a competitive mRNP formation in the 3′UTR ? The mechanism is activated by acute phase stress and inflammation ? The prototypic thrombin links the mechanism to blood coagulation and tumor spread     

Imprinted gene dosage is critical for the transition to independent life

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Highlights? Correct dosage of chromosome 12-imprinted genes is essential for postnatal survival ? Disruption of Dlk1 and Dio3 imprinting causes failure to adapt to independent life ? Maximal brown adipose activity is required as animals first leave the nest ? Dlk1 and Dio3 regulate maturation of brown adipose tissue     

Aurora B regulates formin mDia3 in achieving metaphase chromosome alignment

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Highlights? Involvement of formin mDia3 in stable kinetochore microtubule attachment ? The actin activity of mDia3 is not necessary for metaphase chromosome alignment ? EB1-binding by mDia3 contributes to position chromosomes at the metaphase plate ? Aurora B phosphorylates mDia3 to regulate its microtubule activity