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     

Quiescent and Active Hippocampal Neural Stem Cells with Distinct Morphologies Respond Selectively to Physiological and Pathological Stimuli and Aging

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Highlights? Notch signaling defines morphologically distinct hippocampal stem cell populations ? Radial and horizontal hippocampal stem cells depend on canonical Notch signaling ? Different neural stem cell subpopulations respond selectively to neurogenic stimuli ? Aging results in a reversible transition of stem cells to a quiescent state     

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     

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     

Selective Elimination of Human Pluripotent Stem Cells by an Oleate Synthesis Inhibitor Discovered in a High-Throughput Screen

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Highlights? High-throughput screen identifies selective cytotoxic inhibitors of hPSCs ? The most potent and selective compound inhibits stearoyl-coA desaturase (SCD1) ? Pluripotent cells uniquely depend on oleate metabolism for their viability ? SCD1 inhibition rapidly and robustly eliminates undifferentiated cells from culture     

Spatial Restriction of FGF Signaling by a Matrix Metalloprotease Controls Branching Morphogenesis

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Highlights? Drosophila Matrix Metalloprotease (Mmp) inhibits FGF signaling ? An FGF – MMP feedback loop regulates branching morphogenesis ? Mmp2 spatially regulates FGF signaling in epithelia     

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     

Multiple Epigenetic Modifiers Induce Aggressive Viral Extinction in Extraembryonic Endoderm Stem Cells

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Highlights? Mouse ESCs, TSCs, and XEN cells have different capacities to suppress retroviral activity ? RNAi screens identified epigenetic factors that mediate silencing of retroviruses ? Candidates modulate integrated, as well as endogenous, retroviral element silencing ? An Argonaute protein binds integrated provirus and may mediate retroviral extinction     

Tet Proteins Connect the O-Linked N-acetylglucosamine Transferase Ogt to Chromatin in Embryonic Stem Cells

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Highlights? Ogt forms a complex with Tet1 and Tet2 in the nucleus of embryonic stem cells ? Ogt preferentially associates with promoter regions in proximity of TSS ? Ogt shows >90% of colocalization with Tet1 at methylation-free CpG-rich elements ? Tet1 is required for global Ogt chromatin recruitment regulating its activity     

FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and man

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Highlights? FGF20 and FGF9 are the niche ligands for developing metanephric kidney progenitors ? FGF9 is expressed in duct epithelia; both ligands are expressed by progenitor cells ? FGF20 loss in humans, or FGF9/20 loss in mice, results in kidney agenesis ? FGF9/20 can maintain competence of sorted, pure progenitor cell populations in vitro     

A Pan-BCL2 Inhibitor Renders Bone-Marrow-Resident Human Leukemia Stem Cells Sensitive to Tyrosine Kinase Inhibition

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Highlights? Splice-isoform switching favors prosurvival BCL2 family expression in human BC ? BC LSCs are quiescent and TKI-resistant in the marrow niche ? Sabutoclax, a pan-BCL2 inhibitor, enhances TKI sensitivity of bone marrow BC LSCs     

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     

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     

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     

Integration of Genome-wide Approaches Identifies lncRNAs of Adult Neural Stem Cells and Their Progeny In Vivo

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Highlights? RNA-seq, RNA Capture-Seq of SVZ-NSCs reveals unannotated lncRNAs and splice variants ? lncRNA loci have dynamic chromatin signatures, including bivalency in SVZ-NSCs ? Online resource facilitates discovery of lncRNAs involved in adult neurogenesis ? lncRNAs can regulate glial-neuronal lineage specification of SVZ-NSCs     

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     

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     

Epigenetic Reprogramming of Human Embryonic Stem Cells into Skeletal Muscle Cells and Generation of Contractile Myospheres

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Highlights? hESCs are resistant to MyoD-mediated myogenic conversion ? BAF60C is the limiting factor for activation of skeletal myogenesis in hESCs ? BAF60C instructs MyoD for activation of target genes in hESCs ? Epigenetically committed hESCs are suitable for generation of contractile myospheres     

Uncoupling VEGFA Functions in Arteriogenesis and Hematopoietic Stem Cell Specification

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Highlights? VEGFA short isoform supports endothelial/arterial development of the dorsal aorta ? ETO2 maintains high levels of VEGFA medium and long isoforms in the somites ? VEGFA medium isoform instructs the blood program in blood stem cell precursors ? ETO2 specifies blood stem cells in a non-cell-autonomous manner     

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