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












  • Aging Suppresses Skin-Derived Circulating SDF1 to Promote Full-Thickness Tissue Regeneration.

    abstract::Physicians have observed that surgical wounds in the elderly heal with thinner scars than wounds in young patients. Understanding this phenomenon may reveal strategies for promoting scarless wound repair. We show that full-thickness skin wounds in aged but not young mice fully regenerate. Exposure of aged animals to b...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Nishiguchi MA,Spencer CA,Leung DH,Leung TH

    更新日期:2018-09-25 00:00:00

  • Cell-to-Cell Heterogeneity in p38-Mediated Cross-Inhibition of JNK Causes Stochastic Cell Death.

    abstract::The stress-activated protein kinases c-Jun N-terminal kinase (JNK) and p38 are important players in cell-fate decisions in response to environmental stress signals. Crosstalk signaling between JNK and p38 is emerging as an important regulatory mechanism in inflammatory and stress responses. However, it is unknown how ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Miura H,Kondo Y,Matsuda M,Aoki K

    更新日期:2018-09-04 00:00:00

  • Clonal Heterogeneity Influences the Fate of New Adaptive Mutations.

    abstract::The joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood but essential to designing successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique hap...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Vázquez-García I,Salinas F,Li J,Fischer A,Barré B,Hallin J,Bergström A,Alonso-Perez E,Warringer J,Mustonen V,Liti G

    更新日期:2017-10-17 00:00:00

  • Gli protein activity is controlled by multisite phosphorylation in vertebrate Hedgehog signaling.

    abstract::Gli proteins are transcriptional effectors of the Hedgehog (Hh) pathway in both normal development and cancer. We describe a program of multisite phosphorylation that regulates the conversion of Gli proteins into transcriptional activators. In the absence of Hh ligands, Gli activity is restrained by the direct phospho...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Niewiadomski P,Kong JH,Ahrends R,Ma Y,Humke EW,Khan S,Teruel MN,Novitch BG,Rohatgi R

    更新日期:2014-01-16 00:00:00

  • Degree of recruitment of DOT1L to MLL-AF9 defines level of H3K79 Di- and tri-methylation on target genes and transformation potential.

    abstract::The MLL gene is a common target of chromosomal translocations found in human leukemia. MLL-fusion leukemia has a consistently poor outcome. One of the most common translocation partners is AF9 (MLLT3). MLL-AF9 recruits DOT1L, a histone 3 lysine 79 methyltransferase (H3K79me1/me2/me3), leading to aberrant gene transcri...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kuntimaddi A,Achille NJ,Thorpe J,Lokken AA,Singh R,Hemenway CS,Adli M,Zeleznik-Le NJ,Bushweller JH

    更新日期:2015-05-05 00:00:00

  • Computational Design of Epitope-Specific Functional Antibodies.

    abstract::The ultimate goal of protein design is to introduce new biological activity. We propose a computational approach for designing functional antibodies by focusing on functional epitopes, integrating large-scale statistical analysis with multiple structural models. Machine learning is used to analyze these models and pre...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Nimrod G,Fischman S,Austin M,Herman A,Keyes F,Leiderman O,Hargreaves D,Strajbl M,Breed J,Klompus S,Minton K,Spooner J,Buchanan A,Vaughan TJ,Ofran Y

    更新日期:2018-11-20 00:00:00

  • From Retina to Stem Cell and Back Again: Memories of a Chromatin Journey.

    abstract::The use of retinal organoids requires efficient differentiation from induced pluripotent stem cells (iPSCs). In this issue of Cell Reports, Wang et al. (2018) examine how the chromatin landscape after iPSC programming predicts their ability to differentiate into retinal tissue. ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Roberts JM,Vetter ML

    更新日期:2018-03-06 00:00:00

  • ABCE1 Controls Ribosome Recycling by an Asymmetric Dynamic Conformational Equilibrium.

    abstract::The twin-ATPase ABCE1 has a vital function in mRNA translation by recycling terminated or stalled ribosomes. As for other functionally distinct ATP-binding cassette (ABC) proteins, the mechanochemical coupling of ATP hydrolysis to conformational changes remains elusive. Here, we use an integrated biophysical approach ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Gouridis G,Hetzert B,Kiosze-Becker K,de Boer M,Heinemann H,Nürenberg-Goloub E,Cordes T,Tampé R

    更新日期:2019-07-16 00:00:00

  • Elevated Prolactin during Pregnancy Drives a Phenotypic Switch in Mouse Hypothalamic Dopaminergic Neurons.

    abstract::Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit pr...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Yip SH,Romanò N,Gustafson P,Hodson DJ,Williams EJ,Kokay IC,Martin AO,Mollard P,Grattan DR,Bunn SJ

    更新日期:2019-02-12 00:00:00

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

    abstract::Synapse elimination is crucial for precise neural circuit formation during postnatal development. We examined how relative differences in synaptic strengths among competing inputs and/or absolute synaptic strengths contribute to climbing fiber (CF) to Purkinje cell (PC) synapse elimination in the cerebellum. We genera...

    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

  • IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from γδ T Cells.

    abstract::Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. We report an investigation in cellular targets of IL-38 during the progression of ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Han Y,Mora J,Huard A,da Silva P,Wiechmann S,Putyrski M,Schuster C,Elwakeel E,Lang G,Scholz A,Scholz T,Schmid T,de Bruin N,Billuart P,Sala C,Burkhardt H,Parnham MJ,Ernst A,Brüne B,Weigert A

    更新日期:2019-04-16 00:00:00

  • Pitpnc1a Regulates Zebrafish Sleep and Wake Behavior through Modulation of Insulin-like Growth Factor Signaling.

    abstract::The lipid transporters of the phosphatidylinositol transfer protein (PITP) family dictate phosphoinositide compartmentalization, and specific phosphoinositides play crucial roles in signaling cascades, membrane traffic, ion channel regulation, and actin dynamics. Although PITPs are enriched in the brain, their physiol...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ashlin TG,Blunsom NJ,Ghosh M,Cockcroft S,Rihel J

    更新日期:2018-08-07 00:00:00

  • LRIG1-Mediated Inhibition of EGF Receptor Signaling Regulates Neural Precursor Cell Proliferation in the Neocortex.

    abstract::Here, we ask how neural stem cells (NSCs) transition in the developing neocortex from a rapidly to a slowly proliferating state, a process required to maintain lifelong stem cell pools. We identify LRIG1, known to regulate receptor tyrosine kinase signaling in other cell types, as a negative regulator of cortical NSC ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Jeong D,Lozano Casasbuenas D,Gengatharan A,Edwards K,Saghatelyan A,Kaplan DR,Miller FD,Yuzwa SA

    更新日期:2020-10-13 00:00:00

  • Flow Dynamics and HSPC Homing in Bone Marrow Microvessels.

    abstract::Measurements of flow velocities at the level of individual arterial vessels and sinusoidal capillaries are crucial for understanding the dynamics of hematopoietic stem and progenitor cell homing in the bone marrow vasculature. We have developed two complementary intravital two-photon imaging approaches to determine bl...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Bixel MG,Kusumbe AP,Ramasamy SK,Sivaraj KK,Butz S,Vestweber D,Adams RH

    更新日期:2017-02-14 00:00:00

  • Nutrient-Dependent Trade-Offs between Ribosomes and Division Protein Synthesis Control Bacterial Cell Size and Growth.

    abstract::Cell size control emerges from a regulated balance between the rates of cell growth and division. In bacteria, simple quantitative laws connect cellular growth rate to ribosome abundance. However, it remains poorly understood how translation regulates bacterial cell size and shape under growth perturbations. Here, we ...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Serbanescu D,Ojkic N,Banerjee S

    更新日期:2020-09-22 00:00:00

  • Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response.

    abstract::Recent evidence supports the presence of an L-glutamyl methyltransferase(s) in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as "acidic residue methyltransferase-1" (Armt1), an enzyme that specifically targets prolife...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Perry JJ,Ballard GD,Albert AE,Dobrolecki LE,Malkas LH,Hoelz DJ

    更新日期:2015-03-03 00:00:00

  • Magnitude of Therapeutic STING Activation Determines CD8+ T Cell-Mediated Anti-tumor Immunity.

    abstract::Intratumoral (IT) STING activation results in tumor regression in preclinical models, yet factors dictating the balance between innate and adaptive anti-tumor immunity are unclear. Here, clinical candidate STING agonist ADU-S100 (S100) is used in an IT dosing regimen optimized for adaptive immunity to uncover requirem...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Sivick KE,Desbien AL,Glickman LH,Reiner GL,Corrales L,Surh NH,Hudson TE,Vu UT,Francica BJ,Banda T,Katibah GE,Kanne DB,Leong JJ,Metchette K,Bruml JR,Ndubaku CO,McKenna JM,Feng Y,Zheng L,Bender SL,Cho CY,Leong ML

    更新日期:2018-12-11 00:00:00

  • Brain-State-Dependent Modulation of Neuronal Firing and Membrane Potential Dynamics in the Somatosensory Thalamus during Natural Sleep.

    abstract::The thalamus plays a central role in sleep rhythms in the mammalian brain and, yet, surprisingly little is known about its function and interaction with local cortical oscillations during NREM sleep (NREM). We investigated the neuronal correlates of cortical barrel activity in the two corresponding thalamic nuclei, th...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Urbain N,Fourcaud-Trocmé N,Laheux S,Salin PA,Gentet LJ

    更新日期:2019-02-05 00:00:00

  • A humanized mouse identifies the bone marrow as a niche with low therapeutic IgG activity.

    abstract::Genetic differences between humans and in vivo model systems, including mice and nonhuman primates, make it difficult to predict the efficacy of immunoglobulin G (IgG) activity in humans and understand the molecular and cellular mechanisms underlying that activity. To bridge this gap, we established a small-animal mod...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Lux A,Seeling M,Baerenwaldt A,Lehmann B,Schwab I,Repp R,Meidenbauer N,Mackensen A,Hartmann A,Heidkamp G,Dudziak D,Nimmerjahn F

    更新日期:2014-04-10 00:00:00

  • Functional Specialization of Human Salivary Glands and Origins of Proteins Intrinsic to Human Saliva.

    abstract::Salivary proteins are essential for maintaining health in the oral cavity and proximal digestive tract, and they serve as potential diagnostic markers for monitoring human health and disease. However, their precise organ origins remain unclear. Through transcriptomic analysis of major adult and fetal salivary glands a...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Saitou M,Gaylord EA,Xu E,May AJ,Neznanova L,Nathan S,Grawe A,Chang J,Ryan W,Ruhl S,Knox SM,Gokcumen O

    更新日期:2020-11-17 00:00:00

  • Chronic Corticosterone Elevation Suppresses Adult Hippocampal Neurogenesis by Hyperphosphorylating Huntingtin.

    abstract::Chronic exposure to stress is a major risk factor for neuropsychiatric disease, and elevated plasma corticosterone (CORT) correlates with reduced levels of both brain-derived neurotrophic factor (BDNF) and hippocampal neurogenesis. Precisely how these phenomena are linked, however, remains unclear. Using a cortico-hip...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Agasse F,Mendez-David I,Christaller W,Carpentier R,Braz BY,David DJ,Saudou F,Humbert S

    更新日期:2020-07-07 00:00:00

  • Neuronal Regulation of Schwann Cell Mitochondrial Ca(2+) Signaling during Myelination.

    abstract::Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulat...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Ino D,Sagara H,Suzuki J,Kanemaru K,Okubo Y,Iino M

    更新日期:2015-09-29 00:00:00

  • Mpn1, mutated in poikiloderma with neutropenia protein 1, is a conserved 3'-to-5' RNA exonuclease processing U6 small nuclear RNA.

    abstract::Clericuzio-type poikiloderma with neutropenia (PN) is a rare genodermatosis associated with mutations in the C16orf57 gene, which codes for the uncharacterized protein hMpn1. We show here that, in both fission yeasts and humans, Mpn1 processes the spliceosomal U6 small nuclear RNA (snRNA) posttranscriptionally. In Mpn...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Shchepachev V,Wischnewski H,Missiaglia E,Soneson C,Azzalin CM

    更新日期:2012-10-25 00:00:00

  • Auxilin Underlies Progressive Locomotor Deficits and Dopaminergic Neuron Loss in a Drosophila Model of Parkinson's Disease.

    abstract::Parkinson's disease (PD) is a common neurodegenerative disorder that exhibits motor and non-motor symptoms, as well as pathological hallmarks, including dopaminergic (DA) neuron death and formation of α-synuclein (α-Syn) Lewy bodies. Cyclin-G-associated kinase (GAK), a PD susceptibility gene identified through genome-...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Song L,He Y,Ou J,Zhao Y,Li R,Cheng J,Lin CH,Ho MS

    更新日期:2017-01-31 00:00:00

  • Activation of Mevalonate Pathway via LKB1 Is Essential for Stability of Treg Cells.

    abstract::The function of regulatory T (Treg) cells depends on lipid oxidation. However, the molecular mechanism by which Treg cells maintain lipid metabolism after activation remains elusive. Liver kinase B1 (LKB1) acts as a coordinator by linking cellular metabolism to substrate AMP-activated protein kinase (AMPK). We show th...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Timilshina M,You Z,Lacher SM,Acharya S,Jiang L,Kang Y,Kim JA,Chang HW,Kim KJ,Park B,Song JH,Ko HJ,Park YY,Ma MJ,Nepal MR,Jeong TC,Chung Y,Waisman A,Chang JH

    更新日期:2019-06-04 00:00:00

  • Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling.

    abstract::The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in endothelial cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic signaling to enhance tumor growth. We show that cancer ce...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Balaji Ragunathrao VA,Anwar M,Akhter MZ,Chavez A,Mao Y,Natarajan V,Lakshmikanthan S,Chrzanowska-Wodnicka M,Dudek AZ,Claesson-Welsh L,Kitajewski JK,Wary KK,Malik AB,Mehta D

    更新日期:2019-12-10 00:00:00

  • Gliomas Interact with Non-glioma Brain Cells via Extracellular Vesicles.

    abstract::Emerging evidence suggests that crosstalk between glioma cells and the brain microenvironment may influence brain tumor growth. To date, known reciprocal interactions among these cells have been limited to the release of paracrine factors. Combining a genetic strategy with longitudinal live imaging, we find that indiv...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Gao X,Zhang Z,Mashimo T,Shen B,Nyagilo J,Wang H,Wang Y,Liu Z,Mulgaonkar A,Hu XL,Piccirillo SGM,Eskiocak U,Davé DP,Qin S,Yang Y,Sun X,Fu YX,Zong H,Sun W,Bachoo RM,Ge WP

    更新日期:2020-02-25 00:00:00

  • ATM and SIRT6/SNF2H Mediate Transient H2AX Stabilization When DSBs Form by Blocking HUWE1 to Allow Efficient γH2AX Foci Formation.

    abstract::In response to DNA double-strand breaks (DSBs), H2AX is rapidly phosphorylated at Ser139 to promote DSB repair. Here we show that H2AX is rapidly stabilized in response to DSBs to efficiently generate γH2AX foci. This mechanism operated even in quiescent cells that barely expressed H2AX. H2AX stabilization resulted fr...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Atsumi Y,Minakawa Y,Ono M,Dobashi S,Shinohe K,Shinohara A,Takeda S,Takagi M,Takamatsu N,Nakagama H,Teraoka H,Yoshioka K

    更新日期:2015-12-29 00:00:00

  • Interneuronal Transfer and Distal Action of Tetanus Toxin and Botulinum Neurotoxins A and D in Central Neurons.

    abstract::Recent reports suggest that botulinum neurotoxin (BoNT) A, which is widely used clinically to inhibit neurotransmission, can spread within networks of neurons to have distal effects, but this remains controversial. Moreover, it is not known whether other members of this toxin family are transferred between neurons. He...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Bomba-Warczak E,Vevea JD,Brittain JM,Figueroa-Bernier A,Tepp WH,Johnson EA,Yeh FL,Chapman ER

    更新日期:2016-08-16 00:00:00

  • Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    abstract::Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexi...

    journal_title:Cell reports

    pub_type: 杂志文章


    authors: Kloosterman WP,Tavakoli-Yaraki M,van Roosmalen MJ,van Binsbergen E,Renkens I,Duran K,Ballarati L,Vergult S,Giardino D,Hansson K,Ruivenkamp CA,Jager M,van Haeringen A,Ippel EF,Haaf T,Passarge E,Hochstenbach R,Menten B,

    更新日期:2012-06-28 00:00:00