SIRT3 Reverses Aging-Associated Degeneration

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Highlights? SIRT3 is highly enriched in HSCs and suppressed in differentiated hematopoietic cells ? SIRT3 regulates HSC self-renewal under stress or at an old age ? SIRT3 regulates mitochondrial metabolic homeostasis and reduces ROS in HSCs ? SIRT3 is suppressed with age, and its upregulation rejuvenates aged HSCs     

Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells

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Highlights? PU.1 prevents hematopoietic stem cell (HSC) exhaustion ? PU.1 is a master regulator of cell-cycle genes in HSCs ? PU.1 binding mediates chromosome looping in HSCs ? Positive autoregulation via a ?14 kb enhancer sustains PU.1 levels in HSCs     

Metabolic Regulation by the Mitochondrial Phosphatase PTPMT1 Is Required for Hematopoietic Stem Cell Differentiation

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Highlights? PTPMT1 depletion causes cell cycle delay and differentiation block in HSCs ? The HSC pool in PTPMT1 knockout mice is drastically (～40-fold) expanded ? Mitochondrial metabolism is altered and AMPK is highly activated in knockout HSCs ? PTPMT1 PIP substrates directly enhance fatty-acid-induced activation of UCP2     

Cdc42 Explores the Cell Periphery for Mate Selection in Fission Yeast

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Highlights? Active Cdc42 forms dynamic zones at the periphery of mating S. pombe cells ? This defines a novel exploratory phase, without cell wall synthase exocytosis or growth ? Zone dynamics occur upon exposure to low- but not high-level pheromone ? Mating partner choice is compromised in absence of low-level pheromone signaling     

Endothelial Cells Are Essential for the Self-Renewal and Repopulation of Notch-Dependent Hematopoietic Stem Cells

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Highlights? Coculture with endothelial cells promotes HSC expansion and self-renewal ? Endothelial cell effect on HSCs mediated by Notch signaling ? In vivo, sinusoidal endothelial cells (SECs) express Notch ligands ? Blocking vessel remodeling impairs hematopoietic recovery after irradiation     

Ultrasensitivity in the Regulation of Cdc25C by Cdk1

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Highlights? The response of Cdc25C to Cdk1 in Xenopus egg extracts is ultrasensitive ? The Hill coefficient for the response is astronomical (～11–32) ? Multisite phosphorylation accounts for some of the ultrasensitivity ? The Cdc25C and Wee1A responses account for the bistability of the mitotic trigger     

Proliferation-Dependent Alterations of the DNA Methylation Landscape Underlie Hematopoietic Stem Cell Aging

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Highlights? Locus-specific alterations of the DNA methylome accompany HSC aging ? Methylation changes target genes expressed downstream of HSCs to alter HSC potential ? HSC potential, DNA methylation, and replicative limits depend on divisional history ? Aging and forced proliferation of HSC results in DNA hypermethylation of PRC2 targets     

Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy

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Highlights? We have determined the cryo-EM structures of ORC, ORC-DNA, and ORC-Cdc6-DNA ? We show that ORC is arranged as Orc1:Orc4:Orc5:Orc2:Orc3, with Orc6 binding to Orc2 ? DNA and Cdc6 binding causes large conformational changes in ORC ? Origin DNA is proposed to bind to the interior surface of the crescent-shaped ORC     

A Network Model of the Molecular Organization of Chromatin in Drosophila

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Highlights? DamID identifies 42 previously unknown chromatin proteins ? Binding maps of new and known chromatin components yield a chromatin network model ? The network model predicts functions of most of the 42 new chromatin proteins ? The chromatin protein network is functionally compartmentalized     

Repeated,Long-Term Cycling of Putative Stem Cells between Niches in a Basal Chordate

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Highlights? Identification of a niche for germline and somatic stem cells in a basal chordate ? Stem cells repeatedly migrate between aged or damaged niches into developing niches     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

Unilateral Dampening of Bmp Activity by Nodal Generates Cardiac Left-Right Asymmetry

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Highlights? Cardiac laterality involves Nodal modulating an antimotogenic Bmp activity ? The Nodal target Hyaluronan synthase 2 unilaterally dampens Bmp signaling activity ? Nonmuscle myosin II is positively regulated by Bmp within cardiac tissue ? High levels of nonmuscle myosin II activity reduce cardiac cell motility     

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     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Homeodomain-interacting protein kinase regulates yorkie activity to promote tissue growth

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Highlights? Hipk induces tissues overgrowth and leads to activation of Yki target genes ? Hipk is required for activity of hyperactive Yki ? Hipk kinase function is essential to promote Yki target genes     

The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity,Is Regulated by Phosphorylation

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Highlights? SAMHD1 only exhibits antiviral activity when expressed in noncycling cells ? SAMHD1 is unphosphorylated in noncycling cells ? Reverse genetics revealed that phosphorylated SAMHD1 is repressive for restriction ? SAMHD1 phosphorylation regulates restriction, but not the cellular levels of dNTPs     

Loss of Dickkopf-1 Restores Neurogenesis in Old Age and Counteracts Cognitive Decline

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Highlights? Dkk1 antagonizes Wnt activity in NPCs ? Loss of Dkk1 increases NPCs, neuronal progeny, and neuronal activity in DG ? Loss of Dkk1 has beneficial effects on affective behavior in the tail suspension test ? Loss of Dkk1 in NPCs restores DG neurogenesis and cognition in old age