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     

Epigenetic Regulation of miR-184 by MBD1 Governs Neural Stem Cell Proliferation and Differentiation

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Highlights? MBD1 governs the proliferation and differentiation of neural stem cells (NSCs) ? MBD1 controls the expression of miRNAs, including miR-184, in NSCs ? MiR-184 represses the expression of Numblike ? Numblike rescues the effects of abnormal MBD1 and miR-184 expression     

A Proteomic Characterization of Factors Enriched at Nascent DNA Molecules

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Highlights? A comprehensive resource of replisome and replisome-associated factors ? A putative link between Williams-Beuren syndrome and DNA replication ? SUMO and UQ show opposite concentrations around replisomes ? ZNF24 is a newly identified DNA-replication factor     

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     

ACTL6a Enforces the Epidermal Progenitor State by Suppressing SWI/SNF-Dependent Induction of KLF4

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Highlights? ACTL6a is downregulated during epidermal differentiation ? ACTL6a loss in epidermis causes progenitor loss and terminal differentiation ? ACTL6a is required for repression of KLF4 and other epidermal differentiation genes ? ACTL6a prevents binding of the SWI/SNF complex to differentiation genes     

Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation

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Highlights? Fbxl10 binds to most CpG islands in ESCs ? Fbxl10 recruits Nspc1 and Ring1B to CpG islands ? The Fbxl10, Nspc1, and Ring1B complex is required for H2A monoubiquitylation ? Fbxl10 is required for proper ESC differentiation     

Olig2 Targets Chromatin Remodelers to Enhancers to Initiate Oligodendrocyte Differentiation

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Highlights? Activation of the Brg1 chromatin-remodeling complex drives OPC differentiation ? Olig2 prepatterns and directs Brg1 targeting to oligodendrocyte-specific enhancers ? Functional and stage-dependent Olig2/Brg1 targeting in oligodendrocyte development ? Olig2/Brg1 targeting coupled with epigenetic marking defines oligodendrocyte identity     

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     

PRDM14 Ensures Naive Pluripotency through Dual Regulation of Signaling and Epigenetic Pathways in Mouse Embryonic Stem Cells

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Highlights? Prdm14 expression is important for maintenance of naive pluripotency ? PRDM14 antagonizes FGFR signaling and activates Akt-mTORC1 signaling ? PRDM14 represses de novo DNA methyltransferase expression ? This regulatory input is mediated through recruitment of PRC2     

Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC

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Highlights? Gene expression noise is an efficient means to probe dose responses ? Variability in MYC reveals biphasic E2f1 dose response ? Modeling predicts serum attenuates E2F repression by MYC ? Biphasic expression underlies discrimination of aberrant levels of growth signaling     

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     

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     

Structure of an Asymmetric Ternary Protein Complex Provides Insight for Membrane Interaction

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Highlights? S100A10, annexin A2, and AHNAK are involved in membrane repair ? The AHNAK binding region forms a coiled structure ? Both S100A10 and annexin A2 make contacts to AHNAK and are necessary for binding ? The asymmetric architecture provides a model for AHNAK translocation to the membrane     

Tcf15 Primes Pluripotent Cells for Differentiation

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Highlights? Tcf15 marks a subpopulation of pluripotent cells primed for somatic lineages ? Tcf15 expression is regulated by FGF signaling ? Tcf15 activity is repressed by Id proteins ? Tcf15 represses Nanog and drives differentiation once released from Id inhibition     

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     

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     

The RNA Pol II Elongation Factor Ell3 Marks Enhancers in ES Cells and Primes Future Gene Activation

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Highlights? Ell3 is preferentially found at active, poised, and inactive enhancers in ES cells ? Promoter-proximal Pol II occupancy at key developmental genes requires Ell3 ? Cohesin functions in Ell3-associated enhancer-promoter communication ? Recruitment of P-TEFb within SEC during differentiation is Ell3 dependent     

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     

Axon Regrowth during Development and Regeneration Following Injury Share Molecular Mechanisms

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Highlights? Initial axon outgrowth and regrowth during remodeling are mechanistically distinct ? The nuclear receptor UNF is necessary for axon regrowth but not for initial growth ? TOR is also required for developmental regrowth but not for initial axon outgrowth ? UNF promotes axon regrowth via the TOR pathway and guidance via unknown mechanisms