Transcriptional Signatures of Tau and Amyloid Neuropathology.


:Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.


Cell Rep


Cell reports


Castanho I,Murray TK,Hannon E,Jeffries A,Walker E,Laing E,Baulf H,Harvey J,Bradshaw L,Randall A,Moore K,O'Neill P,Lunnon K,Collier DA,Ahmed Z,O'Neill MJ,Mill J




Has Abstract


2020-02-11 00:00:00












  • Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins.

    abstract::Heterobifunctional proteolysis-targeting chimeric compounds leverage the activity of E3 ligases to induce degradation of target oncoproteins and exhibit potent preclinical antitumor activity. To dissect the mechanisms regulating tumor cell sensitivity to different classes of pharmacological "degraders" of oncoproteins...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shirasaki R,Matthews GM,Gandolfi S,de Matos Simoes R,Buckley DL,Raja Vora J,Sievers QL,Brüggenthies JB,Dashevsky O,Poarch H,Tang H,Bariteau MA,Sheffer M,Hu Y,Downey-Kopyscinski SL,Hengeveld PJ,Glassner BJ,Dhimolea E,O

    更新日期:2021-01-05 00:00:00

  • Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma.

    abstract::Ependymomas exist within distinct genetic subgroups, but the molecular diversity within individual ependymomas is unknown. We perform multiplatform molecular profiling of 6 spatially distinct samples from an ependymoma with C11orf95-RELA fusion. DNA methylation and RNA sequencing distinguish clusters of samples accord...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Liu SJ,Magill ST,Vasudevan HN,Hilz S,Villanueva-Meyer JE,Lastella S,Daggubati V,Spatz J,Choudhury A,Orr BA,Demaree B,Seo K,Ferris SP,Abate AR,Oberheim Bush NA,Bollen AW,McDermott MW,Costello JF,Raleigh DR

    更新日期:2020-02-04 00:00:00

  • A Chemogenetic Tool that Enables Functional Neural Circuit Analysis.

    abstract::Chemogenetics enables manipulation of neuronal activity in experimental animals. While providing information about the transduced neuron expressing a ligand-activated molecule, chemogenetics does not provide understanding about the antecedent circuit that drives that neuron's activity. For current approaches, this is ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ngo HB,Melo MR,Layfield S,Connelly AA,Bassi JK,Xie L,Menuet C,McDougall SJ,Bathgate RAD,Allen AM

    更新日期:2020-09-15 00:00:00

  • p53 Regulates the Expression of LRP1 and Apoptosis through a Stress Intensity-Dependent MicroRNA Feedback Loop.

    abstract::Understanding how p53 activates certain gene programs and not others is critical. Here, we identify low-density lipoprotein receptor-related protein 1 (LRP1), a transmembrane endocytic receptor, as a p53 target gene. We show that, although LRP1 transcript expression is upregulated in response to both sub-lethal and le...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Leslie PL,Franklin DA,Liu Y,Zhang Y

    更新日期:2018-08-07 00:00:00

  • The RNA helicase DHX34 activates NMD by promoting a transition from the surveillance to the decay-inducing complex.

    abstract::Nonsense-mediated decay (NMD) is a surveillance mechanism that degrades aberrant mRNAs. A complex comprising SMG1, UPF1, and the translation termination factors eRF1 and eRF3 (SURF) is assembled in the vicinity of a premature termination codon. Subsequently, an interaction with UPF2, UPF3b, and the exon junction compl...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Hug N,Cáceres JF

    更新日期:2014-09-25 00:00:00

  • Protein Expression Landscape of Mouse Embryos during Pre-implantation Development.

    abstract::Pre-implantation embryo development is an intricate and precisely regulated process orchestrated by maternally inherited proteins and newly synthesized proteins following zygotic genome activation. Although genomic and transcriptomic studies have enriched our understanding of the genetic programs underlying this proce...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Gao Y,Liu X,Tang B,Li C,Kou Z,Li L,Liu W,Wu Y,Kou X,Li J,Zhao Y,Yin J,Wang H,Chen S,Liao L,Gao S

    更新日期:2017-12-26 00:00:00

  • Global scaling down of excitatory postsynaptic responses in cerebellar Purkinje cells impairs developmental synapse elimination.

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    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kawata S,Miyazaki T,Yamazaki M,Mikuni T,Yamasaki M,Hashimoto K,Watanabe M,Sakimura K,Kano M

    更新日期:2014-08-21 00:00:00

  • Developmental Origin of Oligodendrocyte Lineage Cells Determines Response to Demyelination and Susceptibility to Age-Associated Functional Decline.

    abstract::Oligodendrocyte progenitors (OPs) arise from distinct ventral and dorsal domains within the ventricular germinal zones of the embryonic CNS. The functional significance, if any, of these different populations is not known. Using dual-color reporter mice to distinguish ventrally and dorsally derived OPs, we show that, ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Crawford AH,Tripathi RB,Richardson WD,Franklin RJM

    更新日期:2016-04-26 00:00:00

  • Rare Variant Burden Analysis within Enhancers Identifies CAV1 as an ALS Risk Gene.

    abstract::Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. CAV1 and CAV2 organize membrane lipid rafts (MLRs) important for cell signaling and neuronal survival, and overexpression of CAV1 ameliorates ALS phenotypes in vivo. Genome-wide association studies localize a large proportion of ALS risk va...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Cooper-Knock J,Zhang S,Kenna KP,Moll T,Franklin JP,Allen S,Nezhad HG,Iacoangeli A,Yacovzada NY,Eitan C,Hornstein E,Elhaik E,Celadova P,Bose D,Farhan S,Fishilevich S,Lancet D,Morrison KE,Shaw CE,Al-Chalabi A,Projec

    更新日期:2020-12-01 00:00:00

  • PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum.

    abstract::The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp) genes have been identified in the Plasmodium g...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Florentin A,Cobb DW,Fishburn JD,Cipriano MJ,Kim PS,Fierro MA,Striepen B,Muralidharan V

    更新日期:2017-11-14 00:00:00

  • Intestine-to-Germline Transmission of Epigenetic Information Intergenerationally Ensures Systemic Stress Resistance in C. elegans.

    abstract::Changes in epigenetic states affect organismal homeostasis, including stress resistance. However, the mechanisms coordinating epigenetic states and systemic stress resistance remain largely unknown. Here, we identify the intestine-to-germline communication of epigenetic states, which intergenerationally enhances stres...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Nono M,Kishimoto S,Sato-Carlton A,Carlton PM,Nishida E,Uno M

    更新日期:2020-03-10 00:00:00

  • Single-Cell Transcriptional Profiling Reveals Cellular Diversity and Intercommunication in the Mouse Heart.

    abstract::Characterization of the cardiac cellulome, the network of cells that form the heart, is essential for understanding cardiac development and normal organ function and for formulating precise therapeutic strategies to combat heart disease. Recent studies have reshaped our understanding of cardiac cellular composition an...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Skelly DA,Squiers GT,McLellan MA,Bolisetty MT,Robson P,Rosenthal NA,Pinto AR

    更新日期:2018-01-16 00:00:00

  • The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment.

    abstract::Nephrons, the functional units of the kidney, develop from progenitor cells (cap mesenchyme [CM]) surrounding the epithelial ureteric bud (UB) tips. Reciprocal signaling between UB and CM induces nephrogenesis and UB branching. Although low nephron number is implicated in hypertension and renal disease, the mechanisms...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Cebrian C,Asai N,D'Agati V,Costantini F

    更新日期:2014-04-10 00:00:00

  • MALT1 Phosphorylation Controls Activation of T Lymphocytes and Survival of ABC-DLBCL Tumor Cells.

    abstract::The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phosp...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Gehring T,Erdmann T,Rahm M,Graß C,Flatley A,O'Neill TJ,Woods S,Meininger I,Karayel O,Kutzner K,Grau M,Shinohara H,Lammens K,Feederle R,Hauck SM,Lenz G,Krappmann D

    更新日期:2019-10-22 00:00:00

  • Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance.

    abstract::Colorectal cancer (CRC) initiation and growth is often attributed to stem cells, yet little is known about the regulation of these cells. We show here that a subpopulation of Prox1-transcription-factor-expressing cells have stem cell activity in intestinal adenomas, but not in the normal intestine. Using in vivo model...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Wiener Z,Högström J,Hyvönen V,Band AM,Kallio P,Holopainen T,Dufva O,Haglund C,Kruuna O,Oliver G,Ben-Neriah Y,Alitalo K

    更新日期:2014-09-25 00:00:00

  • Voluntary Running Triggers VGF-Mediated Oligodendrogenesis to Prolong the Lifespan of Snf2h-Null Ataxic Mice.

    abstract::Exercise has been argued to enhance cognitive function and slow progressive neurodegenerative disease. Although exercise promotes neurogenesis, oligodendrogenesis and adaptive myelination are also significant contributors to brain repair and brain health. Nonetheless, the molecular details underlying these effects rem...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Alvarez-Saavedra M,De Repentigny Y,Yang D,O'Meara RW,Yan K,Hashem LE,Racacho L,Ioshikhes I,Bulman DE,Parks RJ,Kothary R,Picketts DJ

    更新日期:2016-10-11 00:00:00

  • Facilitates chromatin transcription complex is an "accelerator" of tumor transformation and potential marker and target of aggressive cancers.

    abstract::The facilitates chromatin transcription (FACT) complex is involved in chromatin remodeling during transcription, replication, and DNA repair. FACT was previously considered to be ubiquitously expressed and not associated with any disease. However, we discovered that FACT is the target of a class of anticancer compound...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Garcia H,Miecznikowski JC,Safina A,Commane M,Ruusulehto A,Kilpinen S,Leach RW,Attwood K,Li Y,Degan S,Omilian AR,Guryanova O,Papantonopoulou O,Wang J,Buck M,Liu S,Morrison C,Gurova KV

    更新日期:2013-07-11 00:00:00

  • A Tonoplast P3B-ATPase Mediates Fusion of Two Types of Vacuoles in Petal Cells.

    abstract::It is known that plant cells can contain multiple distinct vacuoles; however, the abundance of multivacuolar cells and the mechanisms underlying vacuolar differentiation and communication among different types of vacuoles remain unknown. PH1 and PH5 are tonoplast P-ATPases that form a heteromeric pump that hyper-acidi...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Faraco M,Li Y,Li S,Spelt C,Di Sansebastiano GP,Reale L,Ferranti F,Verweij W,Koes R,Quattrocchio FM

    更新日期:2017-06-20 00:00:00

  • Single-Cell Transcriptomics of Traced Epidermal and Hair Follicle Stem Cells Reveals Rapid Adaptations during Wound Healing.

    abstract::Epithelial tissues, such as the skin, rely on cellular plasticity of stem cells (SCs) from different niches to restore tissue function after injury. How these molecularly and functionally diverse SC populations respond to injury remains elusive. Here, we genetically labeled Lgr5- or Lgr6-expressing cells from the hair...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Joost S,Jacob T,Sun X,Annusver K,La Manno G,Sur I,Kasper M

    更新日期:2018-10-16 00:00:00

  • The Yeast Prion [SWI(+)] Abolishes Multicellular Growth by Triggering Conformational Changes of Multiple Regulators Required for Flocculin Gene Expression.

    abstract::Although transcription factors are prevalent among yeast prion proteins, the role of prion-mediated transcriptional regulation remains elusive. Here, we show that the yeast prion [SWI(+)] abolishes flocculin (FLO) gene expression and results in a complete loss of multicellularity. Further investigation demonstrates th...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Du Z,Zhang Y,Li L

    更新日期:2015-12-29 00:00:00

  • CISD2 Haploinsufficiency Disrupts Calcium Homeostasis, Causes Nonalcoholic Fatty Liver Disease, and Promotes Hepatocellular Carcinoma.

    abstract::CISD2 is located within the chromosome 4q region frequently deleted in hepatocellular carcinoma (HCC). Mice with Cisd2 heterozygous deficiency develop a phenotype similar to the clinical manifestation of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cisd2 haploinsufficiency causes a...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shen ZQ,Chen YF,Chen JR,Jou YS,Wu PC,Kao CH,Wang CH,Huang YL,Chen CF,Huang TS,Shyu YC,Tsai SF,Kao LS,Tsai TF

    更新日期:2017-11-21 00:00:00

  • Measuring Integrin Conformational Change on the Cell Surface with Super-Resolution Microscopy.

    abstract::We use super-resolution interferometric photoactivation and localization microscopy (iPALM) and a constrained photoactivatable fluorescent protein integrin fusion to measure the displacement of the head of integrin lymphocyte function-associated 1 (LFA-1) resulting from integrin conformational change on the cell surfa...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Moore TI,Aaron J,Chew TL,Springer TA

    更新日期:2018-02-13 00:00:00

  • Allele-Specific DNA Methylation and Its Interplay with Repressive Histone Marks at Promoter-Mutant TERT Genes.

    abstract::A mutation in the promoter of the Telomerase Reverse Transcriptase (TERT) gene is the most frequent noncoding mutation in cancer. The mutation drives unusual monoallelic expression of TERT, allowing immortalization. Here, we find that DNA methylation of the TERT CpG island (CGI) is also allele-specific in multiple can...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Stern JL,Paucek RD,Huang FW,Ghandi M,Nwumeh R,Costello JC,Cech TR

    更新日期:2017-12-26 00:00:00

  • The Ciliary Protein Arl13b Functions Outside of the Primary Cilium in Shh-Mediated Axon Guidance.

    abstract::The small GTPase Arl13b is enriched in primary cilia and regulates Sonic hedgehog (Shh) signaling. During neural development, Shh controls patterning and proliferation through a canonical, transcription-dependent pathway that requires the primary cilium. Additionally, Shh controls axon guidance through a non-canonical...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ferent J,Constable S,Gigante ED,Yam PT,Mariani LE,Legué E,Liem KF Jr,Caspary T,Charron F

    更新日期:2019-12-10 00:00:00

  • Downregulation of a GPCR by β-Arrestin2-Mediated Switch from an Endosomal to a TGN Recycling Pathway.

    abstract::Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone involved in nutrient homeostasis. GIP receptor (GIPR) is constitutively internalized and returned to the plasma membrane, atypical behavior for a G-protein-coupled receptor (GPCR). GIP promotes GIPR downregulation from the plasma membrane by inh...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Abdullah N,Beg M,Soares D,Dittman JS,McGraw TE

    更新日期:2016-12-13 00:00:00

  • Sox9-Positive Progenitor Cells Play a Key Role in Renal Tubule Epithelial Regeneration in Mice.

    abstract::The kidney has a tremendous capacity to regenerate following injury, but factors that govern this response are still largely unknown. We isolated cells from mouse kidneys with high proliferative and multi-lineage differentiation capacity. These cells expressed a high level of Sox9. In regenerating kidneys, Sox9 expres...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kang HM,Huang S,Reidy K,Han SH,Chinga F,Susztak K

    更新日期:2016-02-02 00:00:00

  • Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human.

    abstract::The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kolbe E,Aleithe S,Rennert C,Spormann L,Ott F,Meierhofer D,Gajowski R,Stöpel C,Hoehme S,Kücken M,Brusch L,Seifert M,von Schoenfels W,Schafmayer C,Brosch M,Hofmann U,Damm G,Seehofer D,Hampe J,Gebhardt R,Matz-Soja M

    更新日期:2019-12-24 00:00:00

  • Single-Cell Profiling Defines Transcriptomic Signatures Specific to Tumor-Reactive versus Virus-Responsive CD4+ T Cells.

    abstract::Most current tumor immunotherapy strategies leverage cytotoxic CD8+ T cells. Despite evidence for clinical potential of CD4+ tumor-infiltrating lymphocytes (TILs), their functional diversity limits our ability to harness their activity. Here, we use single-cell mRNA sequencing to analyze the response of tumor-specific...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Magen A,Nie J,Ciucci T,Tamoutounour S,Zhao Y,Mehta M,Tran B,McGavern DB,Hannenhalli S,Bosselut R

    更新日期:2019-12-03 00:00:00

  • Metallothionein 3 Controls the Phenotype and Metabolic Programming of Alternatively Activated Macrophages.

    abstract::Alternatively activated (M2) macrophages promote wound healing but weaken antimicrobial defenses. The mechanisms that enforce macrophage divergence and dictate the phenotypic and metabolic characteristics of M2 macrophages remain elusive. We show that alternative activation with interleukin (IL)-4 induces expression o...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Chowdhury D,Alrefai H,Landero Figueroa JA,Candor K,Porollo A,Fecher R,Divanovic S,Deepe GS Jr,Subramanian Vignesh K

    更新日期:2019-06-25 00:00:00

  • Symmetry Breaking in an Edgeless Epithelium by Fat2-Regulated Microtubule Polarity.

    abstract::Planar cell polarity (PCP) information is a critical determinant of organ morphogenesis. While PCP in bounded epithelial sheets is increasingly well understood, how PCP is organized in tubular and acinar tissues is not. Drosophila egg chambers (follicles) are an acinus-like "edgeless epithelium" and exhibit a continuo...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Chen DY,Lipari KR,Dehghan Y,Streichan SJ,Bilder D

    更新日期:2016-05-10 00:00:00