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     

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     

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     

Inflammatory Chemokines Direct and Restrict Leukocyte Migration within Live Tissues as Glycan-Bound Gradients

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Highlights? Chemokines form tissue-bound gradients in vivo through heparan sulfate proteoglycans ? Chemokines guide neutrophils in vivo as haptotactic gradients ? Chemokines guide neutrophils toward infection loci by triggering orthotaxis ? Chemokines locally restrict neutrophil motility at sites of infection     

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     

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     

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     

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     

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     

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)     

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     

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     

Imparting Regenerative Capacity to Limbs by Progenitor Cell Transplantation

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Highlights? Transplantation of limb progenitor cells promotes multiple digit regenerates ? Wnt/β-catenin activation is required to stimulate adult frog limb regeneration ? Growth factors promote cell survival and growth and give pattern information ? Regeneration-incompetent host limb cells contribute to the regenerated limbs     

Coordinated ciliary beating requires Odf2-mediated polarization of basal bodies via basal feet

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Highlights? Mice expressing truncated Odf2 cough and sneeze due to primary ciliary dyskinesia ? Full-length Odf2 is needed for the formation of basal body-associated basal feet ? In the absence of basal feet, basal bodies fail to align with planar polarity cues ? Polarization of basal bodies by Odf2 is required for coordinated ciliary beating     

Reprogramming Adult Schwann Cells to Stem Cell-like Cells by Leprosy Bacilli Promotes Dissemination of Infection

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Highlights? Leprosy bacteria reprogram adult Schwann cells by altering host-gene expression ? Bacterially reprogrammed cells resemble progenitor/stem-like cells (pSLC) of mesenchymal trait ? pSLC promote bacterial spread to mesenchymal tissues by redifferentiation ? pSLC secrete immune factors, recruit macrophages, transfer bacteria, form granulomas, and disseminate infection     

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