Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid β.

Abstract:

:One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration-based in vivo selection system to generate antibodies that induce cells to both differentiate and selectively localize to different tissues. Here we describe an antibody that induces bone marrow stem cells to differentiate into microglia-like cells that traffic to the brain where they organize into typical networks. Interestingly, in the APP/PS1 Alzheimer's disease mouse model, these induced microglia-like cells are found at sites of plaque formation and significantly reduce their number. These results raise the intriguing question as to whether one can use such antibody-induced differentiation of stem cells to essentially recapitulate embryogenesis in adults to discover cells that can regenerate damaged organ systems.

authors

Han KH,Arlian BM,Macauley MS,Paulson JC,Lerner RA

doi

10.1073/pnas.1719259115

subject

Has Abstract

pub_date

2018-01-16 00:00:00

pages

E372-E381

issue

3

eissn

0027-8424

issn

1091-6490

pii

1719259115

journal_volume

115

pub_type

杂志文章
  • Amphibian development in the virtual absence of gravity.

    abstract::To test whether gravity is required for normal amphibian development, Xenopus laevis females were induced to ovulate aboard the orbiting Space Shuttle. Eggs were fertilized in vitro, and although early embryonic stages showed some abnormalities, the embryos were able to regulate and produce nearly normal larvae. These...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.6.1975

    authors: Souza KA,Black SD,Wassersug RJ

    更新日期:1995-03-14 00:00:00

  • Size-based molecular diagnostics using plasma DNA for noninvasive prenatal testing.

    abstract::Noninvasive prenatal testing using fetal DNA in maternal plasma is an actively researched area. The current generation of tests using massively parallel sequencing is based on counting plasma DNA sequences originating from different genomic regions. In this study, we explored a different approach that is based on the ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1406103111

    authors: Yu SC,Chan KC,Zheng YW,Jiang P,Liao GJ,Sun H,Akolekar R,Leung TY,Go AT,van Vugt JM,Minekawa R,Oudejans CB,Nicolaides KH,Chiu RW,Lo YM

    更新日期:2014-06-10 00:00:00

  • Molecular dissection of the roles of nucleotide binding and hydrolysis in dynein's AAA domains in Saccharomyces cerevisiae.

    abstract::The motor protein cytoplasmic dynein is responsible for most of the minus-end-directed microtubule traffic within cells. Dynein contains four evolutionarily conserved AAA (ATPase associated with various cellular activities) domains that are thought to bind nucleotide; the role of nucleotide binding and hydrolysis in e...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,收录出版

    doi:10.1073/pnas.2637011100

    authors: Reck-Peterson SL,Vale RD

    更新日期:2004-02-10 00:00:00

  • The fatal fungal outbreak on Vancouver Island is characterized by enhanced intracellular parasitism driven by mitochondrial regulation.

    abstract::In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0902963106

    authors: Ma H,Hagen F,Stekel DJ,Johnston SA,Sionov E,Falk R,Polacheck I,Boekhout T,May RC

    更新日期:2009-08-04 00:00:00

  • Spiral structure of Escherichia coli HUalphabeta provides foundation for DNA supercoiling.

    abstract::We determined the crystal structure of the Escherichia coli nucleoid-associated HUalphabeta protein by x-ray diffraction and observed that the heterodimers form multimers with octameric units in three potential arrangements, which may serve specialized roles in different DNA transaction reactions. It is of special imp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611686104

    authors: Guo F,Adhya S

    更新日期:2007-03-13 00:00:00

  • Ergodic and nonergodic processes coexist in the plasma membrane as observed by single-molecule tracking.

    abstract::Diffusion in the plasma membrane of living cells is often found to display anomalous dynamics. However, the mechanism underlying this diffusion pattern remains highly controversial. Here, we study the physical mechanism underlying Kv2.1 potassium channel anomalous dynamics using single-molecule tracking. Our analysis ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1016325108

    authors: Weigel AV,Simon B,Tamkun MM,Krapf D

    更新日期:2011-04-19 00:00:00

  • Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1.

    abstract::Growth factor-induced signals govern the expression of three D-type cyclins, which, in turn, function as regulatory subunits of cyclin-dependent kinases (cdks) to control cell cycle transitions during the late G1 interval. 32D myeloid cells, which self-renew as uncommitted precursors in interleukin 3 (IL-3), express c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.24.11513

    authors: Kato JY,Sherr CJ

    更新日期:1993-12-15 00:00:00

  • Increasing aridity reduces soil microbial diversity and abundance in global drylands.

    abstract::Soil bacteria and fungi play key roles in the functioning of terrestrial ecosystems, yet our understanding of their responses to climate change lags significantly behind that of other organisms. This gap in our understanding is particularly true for drylands, which occupy ∼41% of Earth´s surface, because no global, sy...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1516684112

    authors: Maestre FT,Delgado-Baquerizo M,Jeffries TC,Eldridge DJ,Ochoa V,Gozalo B,Quero JL,García-Gómez M,Gallardo A,Ulrich W,Bowker MA,Arredondo T,Barraza-Zepeda C,Bran D,Florentino A,Gaitán J,Gutiérrez JR,Huber-Sannwald E,Jan

    更新日期:2015-12-22 00:00:00

  • Specificity of short interfering RNA determined through gene expression signatures.

    abstract::Short interfering RNA (siRNA) is widely used for studying gene function and holds great promise as a tool for validating drug targets and treating disease. A critical assumption in these applications is that the effect of siRNA on cells is specific, i.e., limited to the specific knockdown of the target gene. In this a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1131959100

    authors: Semizarov D,Frost L,Sarthy A,Kroeger P,Halbert DN,Fesik SW

    更新日期:2003-05-27 00:00:00

  • Production of a functional eukaryotic enzyme in Escherichia coli: cloning and expression of the yeast structural gene for imidazole-glycerolphosphate dehydratase (his3).

    abstract::A cloned segment of yeast DNA containing the structural gene for imidazoleglycerolphosphate dehydratase (D-erythro-imidazoleglycerolphosphate hydro-lase, EC 4.2.1.19) is transcribed and translated in Escherichia coli with sufficient fidelity to produce functional enzyme. This segment of yeast DNA was isolated as a via...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.12.5255

    authors: Struhl K,Davis RW

    更新日期:1977-12-01 00:00:00

  • The methylotrophic yeast Hansenula polymorpha contains an inducible import pathway for peroxisomal matrix proteins with an N-terminal targeting signal (PTS2 proteins).

    abstract::Two main types of peroxisomal targeting signals have been identified that reside either at the extreme C terminus (PTS1) or the N terminus (PTS2) of the protein. In the methylotrophic yeast Hansenula polymorpha the majority of peroxisomal matrix proteins are of the PTS1 type. Thus far, for H. polymorpha only amine oxi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.26.12985

    authors: Faber KN,Haima P,Gietl C,Harder W,Ab G,Veenhuis M

    更新日期:1994-12-20 00:00:00

  • The zero dispersion limit for the Korteweg-deVries KdV equation.

    abstract::We use the inverse scattering method to determine the weak limit of solutions of the Korteweg-deVries equation as dispersion tends to zero. The limit, valid for all time, is characterized in terms of a quadratic programming problem which can be solved with the aid of function theoretic methods. For large t, the soluti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.76.8.3602

    authors: Lax PD,Levermore CD

    更新日期:1979-08-01 00:00:00

  • Inhibition of tissue damage by the arachidonate lipoxygenase inhibitor BW755C.

    abstract::The effects of three anti-inflammatory drugs, which interfere with arachidonic acid transformation by three different enzymes, have been compared by using a simple model of tissue damage and foreign body rejection. In groups of control rats, subcutaneously implanted polyester sponges were rejected after a mean of 12 d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.9.2890

    authors: Higgs GA,Mugridge KG,Moncada S,Vane JR

    更新日期:1984-05-01 00:00:00

  • Snapshots of a protein folding intermediate.

    abstract::We have investigated the folding dynamics of Thermus thermophilus cytochrome c(552) by time-resolved fluorescence energy transfer between the heme and each of seven site-specific fluorescent probes. We have found both an equilibrium unfolding intermediate and a distinct refolding intermediate from kinetics studies. De...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1221832110

    authors: Yamada S,Bouley Ford ND,Keller GE,Ford WC,Gray HB,Winkler JR

    更新日期:2013-01-29 00:00:00

  • Isolation of a selenium-containing thiolase from Clostridium kluyveri: identification of the selenium moiety as selenomethionine.

    abstract::Clostridium kluyveri grown in the presence of 1 muM Na2(75)SeO3 produces a thiolase that copurifies with 75Se. Based on several criteria, the selenium moiety in this protein is selenomethionine. The 75Se-labeled amino acid in acid hydrolysates of the radioactive protein cochromatographed with authentic selenomethionin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.16.4912

    authors: Hartmanis MG,Stadtman TC

    更新日期:1982-08-01 00:00:00

  • Abiotic hydrogen (H2) sources and sinks near the Mid-Ocean Ridge (MOR) with implications for the subseafloor biosphere.

    abstract::Free hydrogen (H2) is a basal energy source underlying chemosynthetic activity within igneous ocean crust. In an attempt to systematically account for all H2 within young oceanic lithosphere (<10 Ma) near the Mid-Ocean Ridge (MOR), we construct a box model of this environment. Within this control volume, we assess abi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2002619117

    authors: Worman SL,Pratson LF,Karson JA,Schlesinger WH

    更新日期:2020-06-16 00:00:00

  • Conserved behavioral circuits govern high-speed decision-making in wild fish shoals.

    abstract::To evade their predators, animals must quickly detect potential threats, gauge risk, and mount a response. Putative neural circuits responsible for these tasks have been isolated in laboratory studies. However, it is unclear whether and how these circuits combine to generate the flexible, dynamic sequences of evasion ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1809140115

    authors: Hein AM,Gil MA,Twomey CR,Couzin ID,Levin SA

    更新日期:2018-11-27 00:00:00

  • Theory of a class of locally convex vector lattices which include the lebesgue spaces.

    abstract::In this paper is presented the theory of a class of locally convex lattices (L-lattices) of real functions which generalize the classical Lebesgue spaces. The monotone and dominated convergence theorems for convergence almost everywhere and sequential and order completeness of such lattices are established. These resu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.66.2.275

    authors: Bogdanowicz WM

    更新日期:1970-06-01 00:00:00

  • Proteolytic processing of the Alzheimer disease-associated presenilin-1 generates an in vivo substrate for protein kinase C.

    abstract::The majority of familial Alzheimer disease mutations are linked to the recently cloned presenilin (PS) genes, which encode two highly homologous proteins (PS-1 and PS-2). It was shown that the full-length PS-2 protein is phosphorylated constitutively within its N-terminal domain by casein kinases, whereas the PS-1 pro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.10.5349

    authors: Walter J,Grünberg J,Capell A,Pesold B,Schindzielorz A,Citron M,Mendla K,George-Hyslop PS,Multhaup G,Selkoe DJ,Haass C

    更新日期:1997-05-13 00:00:00

  • Accelerated induction of experimental allergic encephalomyelitis in PL/J mice by a non-V beta 8-specific superantigen.

    abstract::Superantigens such as the staphylococcal enterotoxins can play an important role in exacerbation of autoimmune disorders such as experimental allergic encephalomyelitis (EAE) in mice. In fact, superantigens can reactivate EAE in PL/J mice that have been sensitized to rat myelin basic protein (MBP). The T-cell subset p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.13.6082

    authors: Soos JM,Hobeika AC,Butfiloski EJ,Schiffenbauer J,Johnson HM

    更新日期:1995-06-20 00:00:00

  • The displacement field associated with the freezing of a melt and its role in determining crystal growth kinetics.

    abstract::The atomic displacements associated with the freezing of metals and salts are calculated by treating crystal growth as an assignment problem through the use of an optimal transport algorithm. Converting these displacements into timescales based on the dynamics of the bulk liquid, we show that we can predict the activa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1915806117

    authors: Sun G,Hawken A,Harrowell P

    更新日期:2020-02-18 00:00:00

  • Involvement of tyrosine residues located in the carboxyl tail of the human beta 2-adrenergic receptor in agonist-induced down-regulation of the receptor.

    abstract::Chronic exposure of various cell types to adrenergic agonists leads to a decrease in cell surface beta 2-adrenergic receptor (beta 2AR) number. Sequestration of the receptor away from the cell surface as well as a down-regulation of the total number of cellular receptors are believed to contribute to this agonist-medi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.13.5089

    authors: Valiquette M,Bonin H,Hnatowich M,Caron MG,Lefkowitz RJ,Bouvier M

    更新日期:1990-07-01 00:00:00

  • Formation of unconventional standing waves at graphene edges by valley mixing and pseudospin rotation.

    abstract::We investigate the roles of the pseudospin and the valley degeneracy in electron scattering at graphene edges. It is found that they are strongly correlated with charge density modulations of short-wavelength oscillations and slowly decaying beat patterns in the electronic density profile. Theoretical analyses using n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114548108

    authors: Park C,Yang H,Mayne AJ,Dujardin G,Seo S,Kuk Y,Ihm J,Kim G

    更新日期:2011-11-15 00:00:00

  • Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis.

    abstract::Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used. Here, we present a proof-of-concept study to dete...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1408129111

    authors: Calligaris D,Caragacianu D,Liu X,Norton I,Thompson CJ,Richardson AL,Golshan M,Easterling ML,Santagata S,Dillon DA,Jolesz FA,Agar NY

    更新日期:2014-10-21 00:00:00

  • Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells.

    abstract::A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C gamma 2a and C kappa, were substituted by the human C gamma 1 and C kappa by recombining cDNA modules encoding varia...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.10.3439

    authors: Liu AY,Robinson RR,Hellström KE,Murray ED Jr,Chang CP,Hellström I

    更新日期:1987-05-01 00:00:00

  • Modern proteomes contain putative imprints of ancient shifts in trace metal geochemistry.

    abstract::Because of the rise in atmospheric oxygen 2.3 billion years ago (Gya) and the subsequent changes in oceanic redox state over the last 2.3-1 Gya, trace metal bioavailability in marine environments has changed dramatically. Although theorized to have influenced the biological usage of metals leaving discernable genomic ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0605798103

    authors: Dupont CL,Yang S,Palenik B,Bourne PE

    更新日期:2006-11-21 00:00:00

  • Optical mapping of site-directed cleavages on single DNA molecules by the RecA-assisted restriction endonuclease technique.

    abstract::Fluorescence in situ hybridization (FISH) resolution has advanced because newer techniques use increasingly decondensed chromatin. FISH cannot analyze restriction enzyme cutting sites due to limitations of the hybridization and detection technologies. The RecA-assisted restriction endonuclease (RARE) technique cleaves...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.1.165

    authors: Wang YK,Huff EJ,Schwartz DC

    更新日期:1995-01-03 00:00:00

  • Sequence-based association and selection scans identify drug resistance loci in the Plasmodium falciparum malaria parasite.

    abstract::Through rapid genetic adaptation and natural selection, the Plasmodium falciparum parasite--the deadliest of those that cause malaria--is able to develop resistance to antimalarial drugs, thwarting present efforts to control it. Genome-wide association studies (GWAS) provide a critical hypothesis-generating tool for u...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1210585109

    authors: Park DJ,Lukens AK,Neafsey DE,Schaffner SF,Chang HH,Valim C,Ribacke U,Van Tyne D,Galinsky K,Galligan M,Becker JS,Ndiaye D,Mboup S,Wiegand RC,Hartl DL,Sabeti PC,Wirth DF,Volkman SK

    更新日期:2012-08-07 00:00:00

  • Double-stranded RNA induces mRNA degradation in Trypanosoma brucei.

    abstract::Double-stranded RNA (dsRNA) recently has been shown to give rise to genetic interference in Caenorhabditis elegans and also is likely to be the basis for phenotypic cosuppression in plants in certain instances. While constructing a plasmid vector for transfection of trypanosome cells, we serendipitously discovered tha...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.25.14687

    authors: Ngô H,Tschudi C,Gull K,Ullu E

    更新日期:1998-12-08 00:00:00

  • Rapid neural regulation of muscle urokinase-like plasminogen activator as defined by nerve crush.

    abstract::Muscle plasminogen activators (PAs), such as urokinase-like PA and, to a lesser extent, tissue PA, increase dramatically after denervation induced by axotomy. The PA/plasmin system has also been implicated in degradation of specific components of the muscle fiber basement membrane after local activation of plasminogen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.8.2926

    authors: Hantaï D,Rao JS,Festoff BW

    更新日期:1990-04-01 00:00:00