In Vivo HIF-Mediated Reductive Carboxylation Is Regulated by Citrate Levels and Sensitizes VHL-Deficient Cells to Glutamine Deprivation

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Highlights? HIF is necessary and sufficient to induce reductive carboxylation in RCC cell lines ? HIF promotes the reductive carboxylation flux by reducing citrate levels ? HIF-expressing tumors display reductive carboxylation in vivo ? HIF renders RCC cells sensitive to glutaminase inhibition in vitro and in vivo     

MicroRNA-9 Coordinates Proliferation and Migration of Human Embryonic Stem Cell-Derived Neural Progenitors

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Highlights? miR-9 is expressed in hESC-derived early hNPCs and their progeny ? Loss of miR-9 inhibits early hNPC proliferation and delays maturation ? miR-9 knockdown promotes hNPC migration in vitro and in vivo ? Stathmin is a target of miR-9 and mediates its effects in early hNPCs     

PARP1 Represses PAP and Inhibits Polyadenylation during Heat Shock

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Highlights? PARP1 binds and PARylates PAP in vitro, which inhibits its polyadenylation activity ? Polyadenylation is inhibited during heat shock in a PARP1-dependent manner ? PAP is PARylated in vivo during heat shock ? Inhibition of polyadenylation reflects decreased RNA binding by PARylated PAP     

MT1-MMP Is Required for Myeloid Cell Fusion via Regulation of Rac1 Signaling

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Highlights? Myeloid cells fuse during osteoclast and giant cell formation ? MT1-MMP is required for this fusion in vitro and in vivo ? MT1-MMP regulates the GTPase Rac1 through p130Cas binding ? MT1-MMP proteolytic activity is not required     

Sox2 Cooperates with Inflammation-Mediated Stat3 Activation in the Malignant Transformation of Foregut Basal Progenitor Cells

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Highlights? Sox2+ve basal stem/progenitor cells self-renew and differentiate in vitro and in vivo ? Conditional Sox2 overexpression promotes the expansion of basal progenitor cells ? Sox2 cooperates with an inflammatory microenvironment to induce squamous cancer ? Sox2 and Stat3 together transform mouse and human esophageal progenitor cells     

Thrombopoietin-Increased DNA-PK-Dependent DNA Repair Limits Hematopoietic Stem and Progenitor Cell Mutagenesis in Response to DNA Damage

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Highlights? Mpl loss increases γ-irradiation-induced genomic instability in HSPCs ? TPO promotes DNA repair in vitro and in vivo in HSPCs ? TPO increases DNA-PK activity and NHEJ-mediated repair efficiency in HSPCs ? A single TPO injection before mouse TBI limits long-term HSC injury and mutagenesis     

Estimating the Microtubule GTP Cap Size In Vivo

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Highlights? The microtubule (MT) GTP cap is ～750 tubulin subunits in vivo and extends over 1 μm ? EGFP brightness can be calibrated in vivo using GFP-tubulin signals from MTs ? The presence of GTP-tubulin in the MT lattice influences MT shortening and rescue ? MT tip trackers, like EB1, can be highly concentrated at the MT plus end (～100 μM)     

Liver-Derived Systemic Factors Drive β Cell Hyperplasia in Insulin-Resistant States

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Highlights? Circulating nonneuronal factors drive β cell replication in LIRKO mice ? LIRKO serum increases mouse and human islet β cell replication in vitro ? LIRKO serum induces selective β cell replication in vivo ? Hepatocyte-derived factors stimulate mouse and human β cell replication in vitro     

In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures

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Highlights? Modified small-scale ChIP-seq method applicable to small number of cells ? Genome-wide maps of H3K4me3, H3K27me3, H3K27ac, and H2BK20ac of germ cells in vivo ? Identification of active and inactive regulatory elements in germ cells in vivo ? Germ cell H3K27me3 regions are enriched for retrotransposon repeats     

Dynamic Chromatin Remodeling Mediated by Polycomb Proteins Orchestrates Pancreatic Differentiation of Human Embryonic Stem Cells

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Highlights? Pancreatic lineage progression is governed by PcG-dependent chromatin remodeling ? A temporal chromatin signature predicts regulators of pancreatic development ? Endocrine cells differentiated from hESCs in vivo are similar to native human islets ? In vitro-produced malfunctioning endocrine cells exhibit aberrant chromatin structure     

Influenza A Virus Utilizes Suboptimal Splicing to Coordinate the Timing of Infection

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Highlights? Demonstrates how a bicistronic gene can influence biological circuits ? Characterizes potency of innate immune antagonism in vivo ? Demonstrates how host factors can contribute to the timing of a virus life cycle ? Implicates NEP accumulation in the timing of IAV infection     

Uncovering a Region of Heat Shock Protein 90 Important for Client Binding in E. coli and Chaperone Function in Yeast

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Highlights? Using a genetic screen, we selected for defective mutants of E. coli Hsp90 ? The mutants are impaired in ATP-dependent chaperone activity ? The mutations define a client-binding region of E. coli Hsp90 ? Mutation of homologous residues in yeast Hsp90 causes in vivo and in vitro defects     

Differential Regulation of Protrusion and Polarity by PI(3)K during Neutrophil Motility in Live Zebrafish

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Highlights? Neutrophil motility in live zebrafish requires PI(3)K activity at the leading edge ? Localized photo-activation of Rac can to direct migration in vivo ? Rac activation rescues protrusion but not polarization in PI(3)K-inhibited cells ? Separable two-tier regulation of F-actin dynamics and protrusion by PI(3)K     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation     

Proteostasis Modulators Prolong Missense VHL Protein Activity and Halt Tumor Progression

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Highlights? Loss of mutant pVHL in VHL-associated tumors is due to rapid degradation ? Mutant pVHL maintains its intrinsic function as an E3 ligase ? HDACIs stabilize mutant pVHL and ameliorate tumor growth in vivo ? HDACIs represent a targeted therapy for VHL-associated tumors     

A Molecular Motor,KIF13A,Controls Anxiety by Transporting the Serotonin Type 1A Receptor

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Highlights? Kif13a^?/? mice show elevated-anxiety-like behavioral defects ? 5HT_1A receptors are not properly transported in Kif13a^?/? neurons ? The forkhead-associated domain of KIF13A associates directly with 5HT_1A receptors ? KIF13A can translocate 5HT_1A receptors in vivo and in vitro     

Global Changes in the Mammary Epigenome Are Induced by Hormonal Cues and Coordinated by Ezh2

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Highlights? The mammary epigenome is highly sensitive to steroid hormones at specific developmental stages ? Ezh2 links hormonal cues to changes in chromatin structure and gene expression ? Progesterone is a key in vivo regulator of Ezh2 ? Hormone-induced chromatin changes likely play a role in the initiation of breast cancer     

Genomic Regions Flanking E-Box Binding Sites Influence DNA Binding Specificity of bHLH Transcription Factors through DNA Shape

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Highlights? Cbf1 and Tye7 are paralogous TFs with virtually identical DNA binding-site motifs ? The two paralogous TFs bind different genomic target sites in vivo ? The genomic context of putative DNA binding sites affects TF binding specificity ? Structural analyses suggest that genomic context influences TF binding through DNA shape