PPARγ agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein

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Highlights? PPARγ full agonists induce a brown fat phenotype in subcutaneous WAT ? PRDM16 is required for the development of PPARγ agonist-inducible brow adipocytes ? PRDM16 and PPARγ agonists synergistically activate the brown fat gene program ? Browning effect is mediated through the enhanced stability of the PRDM16 protein     

EBF2 Determines and Maintains Brown Adipocyte Identity

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Highlights? Ebf2 is selectively expressed in brown relative to white adipocytes and binds to chromatin at brown fat-specific target sites of Pparγ ? Ebf2 expression in white fat or muscle precursor cells recruits Pparγ to its brown fat-specific gene targets and drives a complete program of brown adipocyte differentiation ? Brown adipose cells and tissue from Ebf2-deficient mice display a complete loss of thermogenic characteristics while gaining molecular attributes of white adipose     

Transcriptional Cofactor TBLR1 Controls Lipid Mobilization in White Adipose Tissue

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Highlights? TBLR1 controls cAMP-dependent lipolysis in adipocytes ? Adipocyte-specific deletion of TBLR1 in mice impairs fasting-induced lipolysis ? Lack of TBLR1 in adipocytes aggravates diet-induced obesity and metabolic dysfunction ? TBLR1 mRNA levels in WAT are elevated under lipolytic conditions in mice and humans     

Comparative Secretome Analyses of Primary Murine White and Brown Adipocytes Reveal Novel Adipokines

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Highlights

• •First comparative proteomic analysis of white and brown adipocyte secretomes.
• •100 novel adipokines differentially secreted from white versus brown adipocytes.
• •Functionally enriched protein class changes in white and brown adipocytes.
• •200 novel, NE-responsive adipokines from brown adipocytes.

     

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     

A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation     

β-Catenin-Driven Binary Fate Specification Segregates Germ Layers in Ascidian Embryos

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Highlights? β-catenin nuclear asymmetry after animal-vegetal-oriented cell divisions ? β-catenin nuclear asymmetry drives binary cell fate choices ? Combinatorial codes of nuclear β-catenin activation segregate ascidian germ layers ? Nuclear β-catenin ON-to-OFF activity is required for marginal mesoderm formation     

Class II Major Histocompatibility Complex Plays an Essential Role in Obesity-Induced Adipose Inflammation

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Highlights? Obesity enhances MHCII expression in primary human and mouse adipocytes ? Adipocytes activate CD4+ ARTs via MHCII and leptin to induce adipose inflammation ? Macrophage changes in adipose follow adipocyte and T cell interactions during HFD ? Adaptive immune mechanisms are essential to obesity-induced adipose inflammation     

p58IPK-Mediated Attenuation of the Proapoptotic PERK-CHOP Pathway Allows Malignant Progression upon Low Glucose

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Highlights? Transformation-associated glucose shortage triggers ER stress ? The ER stress acts as barrier to malignancy by triggering UPR-dependent apoptosis ? p58^IPK expression removes the UPR barrier by attenuating its PERK-CHOP branch ? This adaptive mechanism enables implementation of UPR cytoprotective features     

A Matrix Protein Silences Transposons and Repeats through Interaction with Retinoblastoma-Associated Proteins

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Highlights? The Arabidopsis matrix protein TEK silences transposons and repeat-containing genes ? Binding of TEK on targets affects chromatin conformation and histone modifications ? TEK protein associates with FVE/MSI5-containing histone deacetylation complex ? TEK directs repressive modification as a key structural component in gene silencing     

Regeneration of Human Tumor Antigen-Specific T Cells from iPSCs Derived from Mature CD8+ T Cells

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Highlights? iPSCs generated from T cells specific for the MART-1 melanoma epitope ? Differentiation of iPSCs into T cells with a MART-1 specific T cell receptor ? MART-1-based stimulation of T cells demonstrates retained antigen specificity     

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     

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     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

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     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation