Individually addressable and dynamic DNA gates for multiplexed cell sorting.

Abstract:

:The ability to analyze and isolate cells based on the expression of specific surface markers has increased our understanding of cell biology and produced numerous applications for biomedicine. However, established cell-sorting platforms rely on labels that are limited in number due to biophysical constraints, such as overlapping emission spectra of fluorophores in FACS. Here, we establish a framework built on a system of orthogonal and extensible DNA gates for multiplexed cell sorting. These DNA gates label target cell populations by antibodies to allow magnetic bead isolation en masse and then selectively unlock by strand displacement to sort cells. We show that DNA gated sorting (DGS) is triggered to completion within minutes on the surface of cells and achieves target cell purity, viability, and yield equivalent to that of commercial magnetic sorting kits. We demonstrate multiplexed sorting of three distinct immune cell populations (CD8+, CD4+, and CD19+) from mouse splenocytes to high purity and show that recovered CD8+ T cells retain proliferative potential and target cell-killing activity. To broaden the utility of this platform, we implement a double positive sorting scheme using DNA gates on peptide-MHC tetramers to isolate antigen-specific CD8+ T cells from mice infected with lymphocytic choriomeningitis virus (LCMV). DGS can potentially be expanded with fewer biophysical constraints to large families of DNA gates for applications that require analysis of complex cell populations, such as host immune responses to disease.

authors

Dahotre SN,Chang YM,Wieland A,Stammen SR,Kwong GA

doi

10.1073/pnas.1714820115

subject

Has Abstract

pub_date

2018-04-24 00:00:00

pages

4357-4362

issue

17

eissn

0027-8424

issn

1091-6490

pii

1714820115

journal_volume

115

pub_type

杂志文章
  • Dystrophin protects the sarcolemma from stresses developed during muscle contraction.

    abstract::The protein dystrophin, normally found on the cytoplasmic surface of skeletal muscle cell membranes, is absent in patients with Duchenne muscular dystrophy as well as mdx (X-linked muscular dystrophy) mice. Although its primary structure has been determined, the precise functional role of dystrophin remains the subjec...

    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.90.8.3710

    authors: Petrof BJ,Shrager JB,Stedman HH,Kelly AM,Sweeney HL

    更新日期:1993-04-15 00:00:00

  • High molecular weight polypeptides (270,000-340,000) from cultured cells are related to hog brain microtubule-associated proteins but copurify with intermediate filaments.

    abstract::High molecular weight polypeptides (HMWPs) of 270,000 to 340,000 were found to be major components of intermediate filaments prepared by Triton X-100 extraction after spreading of rat glioma C6, HeLa, Chinese hamster ovary, and simian virus 40-transformed Chinese hamster lung cells. C6 HMWPs were shown to resemble hig...

    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.77.8.4808

    authors: Pytela R,Wiche G

    更新日期:1980-08-01 00:00:00

  • Accessing key steps of human tumor progression in vivo by using an avian embryo model.

    abstract::Experimental in vivo tumor models are essential for comprehending the dynamic process of human cancer progression, identifying therapeutic targets, and evaluating antitumor drugs. However, current rodent models are limited by high costs, long experimental duration, variability, restricted accessibility to the tumor, 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.0408622102

    authors: Hagedorn M,Javerzat S,Gilges D,Meyre A,de Lafarge B,Eichmann A,Bikfalvi A

    更新日期:2005-02-01 00:00:00

  • Intersheet rearrangement of polypeptides during nucleation of {beta}-sheet aggregates.

    abstract::Many neurodegenerative diseases are characterized by the accumulation of amyloid fibers in the brain, which can occur when a protein misfolds into an extended beta-sheet conformation. The nucleation of these beta-sheet aggregates is of particular interest, not only because it is the rate-determining step toward fiber ...

    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.0502804102

    authors: Petty SA,Decatur SM

    更新日期:2005-10-04 00:00:00

  • Modified recombination and transmission of mitochondrial genetic markers in rho minus mutants of Saccharomyces cerevisiae.

    abstract::A large number of primary petite (rho-) clones were isolated after ethidium bromide mutagenesis of various grande (rho+) strains of S. cerevisiae that contained the mitochondrial genetic markers, CR, ER, OIR (or OIIR), and PR. From the frequency of coretention of markers in the petites, we have deduced a probable circ...

    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.73.12.4608

    authors: Boltin-Fukuhara M,Fukuhara H

    更新日期:1976-12-01 00:00:00

  • Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production.

    abstract::Translation of injected mRNA in oocytes of Xenopus laevis has been used as a highly sensitive and quantitative assay for interferon mRNA. Injection into oocytes of polyadenylylated RNA extracted from poly(I).poly(C)-induced human diploid fibroblasts (FS-4) leads to the synthesis of biologically active human fibroblast...

    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.74.8.3409

    authors: Sehgal PB,Dobberstein B,Tamm I

    更新日期:1977-08-01 00:00:00

  • Mechanisms of Kirsten murine sarcoma virus transformation-induced changes in the collagen phenotype and synthetic rate of BALB 3T3 cells.

    abstract::Specific viral transformation rather than cell selection can explain the previously observed increase in the proportion of type III procollagen compared to type I procollagen in BALB 3T3 cells transformed by Kirsten murine sarcoma virus (Ki-MSV). Two subclones of BALB 3T3 A31 were productively infected with with a tem...

    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.78.10.6028

    authors: Bateman JF,Peterkofsky B

    更新日期:1981-10-01 00:00:00

  • Topological knots and links in proteins.

    abstract::Twenty years after their discovery, knots in proteins are now quite well understood. They are believed to be functionally advantageous and provide extra stability to protein chains. In this work, we go one step further and search for links-entangled structures, more complex than knots, which consist of several compone...

    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.1615862114

    authors: Dabrowski-Tumanski P,Sulkowska JI

    更新日期:2017-03-28 00:00:00

  • Bioinspired micrograting arrays mimicking the reverse color diffraction elements evolved by the butterfly Pierella luna.

    abstract::Recently, diffraction elements that reverse the color sequence normally observed in planar diffraction gratings have been found in the wing scales of the butterfly Pierella luna. Here, we describe the creation of an artificial photonic material mimicking this reverse color-order diffraction effect. The bioinspired sys...

    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.1412240111

    authors: England G,Kolle M,Kim P,Khan M,Muñoz P,Mazur E,Aizenberg J

    更新日期:2014-11-04 00:00:00

  • Integration of light and abscisic acid signaling during seed germination and early seedling development.

    abstract::Seed germination is regulated by endogenous hormonal cues and external environmental stimuli such as water, low temperature, and light. After germination, the young seedling must rapidly establish its root system and the photoautotrophic capability appropriate to its surrounding environment. Light and the phytohormone...

    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.0710778105

    authors: Chen H,Zhang J,Neff MM,Hong SW,Zhang H,Deng XW,Xiong L

    更新日期:2008-03-18 00:00:00

  • A labile inhibitor blocks immunoglobulin kappa-light-chain-gene transcription in a pre-B leukemic cell line.

    abstract::The murine pre-B leukemic cell line 70Z/3 contains both an unrearranged immunoglobulin kappa-light-chain gene and a functionally rearranged but silent kappa-light-chain gene. Mitogenic stimulation of growing 70Z/3 cells with bacterial lipopolysaccharide (LPS) activates kappa-light-gene transcription and results in a 1...

    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.83.2.295

    authors: Wall R,Briskin M,Carter C,Govan H,Taylor A,Kincade P

    更新日期:1986-01-01 00:00:00

  • The energy of substituted ethanes. Asymmetry orbitals.

    abstract::The leading terms in the energy of a general substituted ethane are derived in explicit form as a function of the torsional angle theta, the substituent electronegativities, and their mutual overlaps. The energy is found to be the sum of all four overlaps between pairs of asymmetry orbitals, and satisfies the requisit...

    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.70.2.531

    authors: Salem L,Hoffmann R,Otto P

    更新日期:1973-02-01 00:00:00

  • The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization.

    abstract::Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. The function of DJ-1 is unknown, but an acidic isoform accumulates after oxidative stress, leading to the suggestion that DJ-1 is protective under these conditions. We addressed whether this represents a posttranslational modification at cystei...

    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.0402959101

    authors: Canet-Avilés RM,Wilson MA,Miller DW,Ahmad R,McLendon C,Bandyopadhyay S,Baptista MJ,Ringe D,Petsko GA,Cookson MR

    更新日期:2004-06-15 00:00:00

  • Aggregation propensities of superoxide dismutase G93 hotspot mutants mirror ALS clinical phenotypes.

    abstract::Protein framework alterations in heritable Cu, Zn superoxide dismutase (SOD) mutants cause misassembly and aggregation in cells affected by the motor neuron disease ALS. However, the mechanistic relationship between superoxide dismutase 1 (SOD1) mutations and human disease is controversial, with many hypotheses postul...

    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.1308531111

    authors: Pratt AJ,Shin DS,Merz GE,Rambo RP,Lancaster WA,Dyer KN,Borbat PP,Poole FL 2nd,Adams MW,Freed JH,Crane BR,Tainer JA,Getzoff ED

    更新日期:2014-10-28 00:00:00

  • Molecular comparison of alpha 1- and alpha 2-adrenergic receptors suggests that these proteins are structurally related "isoreceptors".

    abstract::The structures of human platelet alpha 2-adrenergic receptors and rat liver alpha 1-adrenergic receptors were compared by utilizing isoelectric focusing, NaDodSO4/PAGE, and monoclonal antibody crossreactivity. Digitonin-solubilized alpha 1- and alpha 2-adrenergic receptors have an identical isoelectric point of 4.6. 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.82.14.4842

    authors: Shreeve SM,Fraser CM,Venter JC

    更新日期:1985-07-01 00:00:00

  • Phytochrome regulates translation of mRNA in the cytosol.

    abstract::An array of photoreceptors including cryptochromes, phototropin, and phytochromes regulates various light responses in plants. Among these photoreceptors, phytochromes perceive red and far-red light by switching between two interconvertible spectral forms (Pr and Pfr). The Pfr form promotes light responses partly by 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.1109683109

    authors: Paik I,Yang S,Choi G

    更新日期:2012-01-24 00:00:00

  • Immortalized keratinocyte lines derived from human embryonic stem cells.

    abstract::Cells of the human embryonic stem (hES) cell line H9, when cultured in the form of embryoid bodies, give rise to cells with markers of the keratinocyte of stratified squamous epithelia. Keratinocytes also form in nodules produced in scid mice by injected H9 cells; the hES-derived keratinocytes could be recovered in cu...

    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.0510953103

    authors: Iuchi S,Dabelsteen S,Easley K,Rheinwald JG,Green H

    更新日期:2006-02-07 00:00:00

  • Clostridioides difficile infection damages colonic stem cells via TcdB, impairing epithelial repair and recovery from disease.

    abstract::Gastrointestinal infections often induce epithelial damage that must be repaired for optimal gut function. While intestinal stem cells are critical for this regeneration process [R. C. van der Wath, B. S. Gardiner, A. W. Burgess, D. W. Smith, PLoS One 8, e73204 (2013); S. Kozar et al., Cell Stem Cell 13, 626-633 (2013...

    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.1915255117

    authors: Mileto SJ,Jardé T,Childress KO,Jensen JL,Rogers AP,Kerr G,Hutton ML,Sheedlo MJ,Bloch SC,Shupe JA,Horvay K,Flores T,Engel R,Wilkins S,McMurrick PJ,Lacy DB,Abud HE,Lyras D

    更新日期:2020-04-07 00:00:00

  • Mitochondrial carbonic anhydrase.

    abstract::We have assayed carbonic anhydrase activity (carbonate dehydratase, carbonate hydro-lyase, EC 4.2.1.1) and bicarbonate permeability in suspensions of broken and intact guinea pig mitochondria by monitoring the disappearance of C16O18O. We found significant activity in preparations from liver and skeletal muscle, but 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.77.9.5562

    authors: Dodgson SJ,Forster RE 2nd,Storey BT,Mela L

    更新日期:1980-09-01 00:00:00

  • Stable three-dimensional metallic carbon with interlocking hexagons.

    abstract::Design and synthesis of 3D metallic carbon that is stable under ambient conditions has been a long-standing dream. We predict the existence of such phases, T6- and T14-carbon, consisting of interlocking hexagons. Their dynamic, mechanical, and thermal stabilities are confirmed by carrying out a variety of state-of-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.1311028110

    authors: Zhang S,Wang Q,Chen X,Jena P

    更新日期:2013-11-19 00:00:00

  • Spoken word production: a theory of lexical access.

    abstract::A core operation in speech production is the preparation of words from a semantic base. The theory of lexical access reviewed in this article covers a sequence of processing stages beginning with the speaker's focusing on a target concept and ending with the initiation of articulation. The initial stages of preparatio...

    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.231459498

    authors: Levelt WJ

    更新日期:2001-11-06 00:00:00

  • Terminal attack trajectories of peregrine falcons are described by the proportional navigation guidance law of missiles.

    abstract::The ability to intercept uncooperative targets is key to many diverse flight behaviors, from courtship to predation. Previous research has looked for simple geometric rules describing the attack trajectories of animals, but the underlying feedback laws have remained obscure. Here, we use GPS loggers and onboard video ...

    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.1714532114

    authors: Brighton CH,Thomas ALR,Taylor GK

    更新日期:2017-12-19 00:00:00

  • Regulation of adenylate cyclase activity mediated by muscarinic acetylcholine receptors.

    abstract::Carbachol, an activator of muscarinic acetylcholine receptors of NG108-15 hybrid cells, inhibits adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] rapidly and reversibly and slowly evokes a 200-300% increase in adenylate cyclase activity over a period of 24-30 hr. Both the inhibition of adenylate cyc...

    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.75.4.1788

    authors: Nathanson NM,Klein WL,Nirenberg M

    更新日期:1978-04-01 00:00:00

  • Membrane-mobility agent-promoted fusion of erythrocytes: fusibility is correlated with attack by calcium-activated cytoplasmic proteases on membrane proteins.

    abstract::Rat, but not human, erythrocytes undergo fusion promoted by the membrane-mobility agent 2-(2-methoxyethoxy)-ethyl cis-8-(2-octylcyclopropyl)octanoate (A2C). The difference in behavior is correlated with rat erythrocyte membrane protein degradation caused by Ca2+-activated proteases. The human erythrocyte is deficient ...

    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.80.24.7542

    authors: Kosower NS,Glaser T,Kosower EM

    更新日期:1983-12-01 00:00:00

  • Mutations that alter the transmission of chloroplast genes in Chlamydomonas.

    abstract::Two mutations are described that alter the pattern of inheritance of chloroplast genes in Chlamydomonas. The mutant gene mat-1 linked to the mating type allele mt(-) greatly increases the frequency of exceptional zygotes, i.e., zygotes that transmit chloroplast genes from the mt(-) (male) parent. In some crosses, 80-9...

    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.71.12.4698

    authors: Sager R,Ramanis Z

    更新日期:1974-12-01 00:00:00

  • Insights into the origin of carbonaceous chondrite organics from their triple oxygen isotope composition.

    abstract::Dust grains of organic matter were the main reservoir of C and N in the forming Solar System and are thus considered to be an essential ingredient for the emergence of life. However, the physical environment and the chemical mechanisms at the origin of these organic grains are still highly debated. In this study, we r...

    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.1808101115

    authors: Tartèse R,Chaussidon M,Gurenko A,Delarue F,Robert F

    更新日期:2018-08-21 00:00:00

  • Immunization with hepatitis C virus-like particles protects mice from recombinant hepatitis C virus-vaccinia infection.

    abstract::We have recently demonstrated that immunization with hepatitis C virus-like particles (HCV-LPs) generated in insect cells can elicit both humoral and cellular immune responses in BALB/c mice. Here, we evaluate the immunogenicity of HCV-LPs in HLA2.1 transgenic (AAD) mice in comparison to DNA immunization. HCV-LP immun...

    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.1131929100

    authors: Murata K,Lechmann M,Qiao M,Gunji T,Alter HJ,Liang TJ

    更新日期:2003-05-27 00:00:00

  • Passage of phenotypes of chemically transformed cells via transfection of DNA and chromatin.

    abstract::DNA was prepared from 15 different mouse and rat cell lines transformed by chemical carcinogens in vitro and in vivo. These DNAs were applied to NIH3T3 mouse fibroblast cultures by using the calcium phosphate transfection technique. DNAs of five donor lines were able to induce foci on the recipient monolayers. Ten oth...

    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.76.11.5714

    authors: Shih C,Shilo BZ,Goldfarb MP,Dannenberg A,Weinberg RA

    更新日期:1979-11-01 00:00:00

  • Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.

    abstract::Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. An acute increase in tumor oxygenation before radiation treatment should therefore significantly improve the tumor cell kill after radiation. Efforts to increase oxygen delivery to the tumor have not shown positiv...

    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.1808945115

    authors: Benej M,Hong X,Vibhute S,Scott S,Wu J,Graves E,Le QT,Koong AC,Giaccia AJ,Yu B,Chen CS,Papandreou I,Denko NC

    更新日期:2018-10-16 00:00:00

  • Binding of the phytotoxin zinniol stimulates the entry of calcium into plant protoplasts.

    abstract::Zinniol [1,2-bis(hydroxymethyl)-3-methoxy-4-methyl-5-(3-methyl-2-butenyloxy)benzene], a toxin produced by fungi of the Alternaria group, causes symptoms in plants that resemble those induced by the fungi. The phytotoxin binds to carrot protoplasts and isolated membranes in a saturable and reversible manner. Receptor o...

    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.85.16.5932

    authors: Thuleau P,Graziana A,Rossignol M,Kauss H,Auriol P,Ranjeva R

    更新日期:1988-08-01 00:00:00