Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet+ B cells.
Abstract: Traditional laboratory model organisms represent a small fraction of the diversity of multicellular life, and findings in any given experimental model often do not translate to other species. Immunology research in non-traditional model organisms can be advantageous or even necessary, such as when studying host-pathogen interactions. However, such research presents multiple challenges, many stemming from an incomplete understanding of potentially species-specific immune cell types, frequencies, and phenotypes. Identifying and characterizing immune cells in such organisms is frequently limited by the availability of species-reactive immunophenotyping reagents for flow cytometry, and insufficient prior knowledge of cell type-defining markers. Here, we demonstrate the utility of single-cell RNA sequencing (scRNA-Seq) to characterize immune cells for which traditional experimental tools are limited. Specifically, we used scRNA-Seq to comprehensively define the cellular diversity of equine peripheral blood mononuclear cells (PBMC) from healthy horses across different breeds, ages, and sexes. We identified 30 cell type clusters partitioned into five major populations: monocytes/dendritic cells, B cells, CD3PRF1 lymphocytes, CD3PRF1 lymphocytes, and basophils. Comparative analyses revealed many cell populations analogous to human PBMC, including transcriptionally heterogeneous monocytes and distinct dendritic cell subsets (cDC1, cDC2, plasmacytoid DC). Remarkably, we found that a majority of the equine peripheral B cell compartment is comprised of T-bet B cells, an immune cell subpopulation typically associated with chronic infection and inflammation in human and mouse. Taken together, our results demonstrate the potential of scRNA-Seq for cellular analyses in non-traditional model organisms and form the basis for an immune cell atlas of horse peripheral blood.
Publication Date: 2021-01-22 PubMed ID: 33482825PubMed Central: PMC7820527DOI: 10.1186/s12915-020-00947-5Google Scholar: Lookup
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- Journal Article
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Summary
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This research presents a deep study of the diversity of immune cells in the blood of healthy horses, using a method known as single-cell RNA sequencing (scRNA-Seq). A significant find was a high proportion of T-bet B cells, usually associated with chronic infection and inflammation in humans and mice.
Background
- The research provides context that traditional laboratory model organisms only reflect a small part of multicellular life diversity. Hence, results from experiments on one model organism often do not translate to other species.
- Immunology research in non-traditional model organisms can offer great benefits, particularly when studying host-pathogen interactions.
- However, there are also numerous challenges therein, primarily stemming from an incomplete understanding of possibly species-specific immune cell types, frequencies, and phenotypes.
- Identifying and characterizing immune cells in such organisms are often hampered by the limited availability of species-reactive immunophenotyping reagents for flow cytometry and inadequate prior knowledge of cell type-defining markers.
Methodology
- In this study, researchers use single-cell RNA sequencing (scRNA-Seq), a next generation sequencing method, to accurately characterize immune cells where traditional experimental tools fall short.
- Specifically, they utilized scRNA-Seq to define the cellular diversity of equine peripheral blood mononuclear cells (PBMC) from healthy horses across a variety of breeds, ages, and sexes.
Results
- The researchers identified 30 cell type clusters that were organized into five major populations: monocytes/dendritic cells, B cells, CD3PRF1 lymphocytes, CD3PRF1 lymphocytes, and basophils.
- Comparative analyses revealed many cell populations similar to human PBMC, including transcriptionally heterogeneous monocytes and distinct subsets of dendritic cells (cDC1, cDC2, plasmacytoid DC).
- The most striking find was that the majority of the equine peripheral B cell compartment contains T-bet B cells. This subpopulation of immune cells is typically connected with chronic infection and inflammation in humans and mice.
Conclusion
- The results of this study offer a demonstration of the potential usefulness of scRNA-Seq for cellular analyses in non-traditional model organisms.
- The findings also lay the foundation for creating an immune cell atlas of horse peripheral blood, which could open the doors for more in-depth and varied immunology studies in equine and other non-traditional organisms.
Cite This Article
APA
Patel RS, Tomlinson JE, Divers TJ, Van de Walle GR, Rosenberg BR.
(2021).
Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet+ B cells.
BMC Biol, 19(1), 13.
https://doi.org/10.1186/s12915-020-00947-5 Publication
Researcher Affiliations
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA.
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Place, New York, NY, 10029, USA. brad.rosenberg@mssm.edu.
MeSH Terms
- Animals
- B-Lymphocytes / classification
- Horses / blood
- Leukocytes, Mononuclear / classification
- Leukocytes, Mononuclear / metabolism
- Sequence Analysis, RNA / veterinary
- Single-Cell Analysis / veterinary
Grant Funding
- K08 AI141767 / NIAID NIH HHS
- S10 OD026880 / NIH HHS
- K08AI141767 / National Institute of Allergy and Infectious Diseases
- 2016-67015-24765 / USDA National institute of Food and Agriculture
- S10 OD018522 / NIH HHS
- S10 OD026880 / NIH HHS
Conflict of Interest Statement
The authors declare no competing interests.
References
This article includes 100 references
- Masopust D, Sivula CP, Jameson SC. Of Mice, Dirty Mice, and Men: Using Mice To Understand Human Immunology.. J Immunol 2017 Jul 15;199(2):383-388.
- Swearengen JR. Choosing the right animal model for infectious disease research.. Animal Model Exp Med 2018 Jun;1(2):100-108.
- Hein WR, Griebel PJ. A road less travelled: large animal models in immunological research.. Nat Rev Immunol 2003 Jan;3(1):79-84.
- Ryu S, Kim BI, Lim JS, Tan CS, Chun BC. One Health Perspectives on Emerging Public Health Threats.. J Prev Med Public Health 2017 Nov;50(6):411-414.
- OneHealth: OIE - World Organisation for Animal Health. https://www.oie.int/en/for-the-media/onehealth/. Accessed 27 Mar 2020.
- One Health | CDC. 2020. https://www.cdc.gov/onehealth/index.html. Accessed 27 Mar 2020.
- Adan A, Alizada G, Kiraz Y, Baran Y, Nalbant A. Flow cytometry: basic principles and applications.. Crit Rev Biotechnol 2017 Mar;37(2):163-176.
- Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project.. Nat Rev Immunol 2012 Feb 17;12(3):191-200.
- Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K, Goldman M, Tirosh I, Bialas AR, Kamitaki N, Martersteck EM, Trombetta JJ, Weitz DA, Sanes JR, Shalek AK, Regev A, McCarroll SA. Highly Parallel Genome-wide Expression Profiling of Individual Cells Using Nanoliter Droplets.. Cell 2015 May 21;161(5):1202-1214.
- Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A, Li V, Peshkin L, Weitz DA, Kirschner MW. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells.. Cell 2015 May 21;161(5):1187-1201.
- Zheng GX, Terry JM, Belgrader P, Ryvkin P, Bent ZW, Wilson R, Ziraldo SB, Wheeler TD, McDermott GP, Zhu J, Gregory MT, Shuga J, Montesclaros L, Underwood JG, Masquelier DA, Nishimura SY, Schnall-Levin M, Wyatt PW, Hindson CM, Bharadwaj R, Wong A, Ness KD, Beppu LW, Deeg HJ, McFarland C, Loeb KR, Valente WJ, Ericson NG, Stevens EA, Radich JP, Mikkelsen TS, Hindson BJ, Bielas JH. Massively parallel digital transcriptional profiling of single cells.. Nat Commun 2017 Jan 16;8:14049.
- Stubbington MJT, Rozenblatt-Rosen O, Regev A, Teichmann SA. Single-cell transcriptomics to explore the immune system in health and disease.. Science 2017 Oct 6;358(6359):58-63.
- Felippe MJB. Equine clinical immunology. Ames: Chichester West Sussex: Wiley; 2016.
- Rosenkrantz W. Immune-mediated dermatoses.. Vet Clin North Am Equine Pract 2013 Dec;29(3):607-13.
- Steinbach F, Deeg C, Mauel S, Wagner B. Equine immunology: offspring of the serum horse.. Trends Immunol 2002 May;23(5):223-5.
- Khurana SK. Zoonotic pathogens transmitted from equines: diagnosis and control. Adv Anim Vet Sci 2015;3:32–53.
- Ramsay JD, Evanoff R, Wilkinson TE Jr, Divers TJ, Knowles DP, Mealey RH. Experimental transmission of equine hepacivirus in horses as a model for hepatitis C virus.. Hepatology 2015 May;61(5):1533-46.
- Tomlinson JE, Wagner B, Felippe MJB, Van de Walle GR. Multispectral fluorescence-activated cell sorting of B and T cell subpopulations from equine peripheral blood.. Vet Immunol Immunopathol 2018 May;199:22-31.
- Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation.. Sci Transl Med 2019 Nov 27;11(520).
- Knox JJ, Myles A, Cancro MP. T-bet(+) memory B cells: Generation, function, and fate.. Immunol Rev 2019 Mar;288(1):149-160.
- Zhang X, Li T, Liu F, Chen Y, Yao J, Li Z, Huang Y, Wang J. Comparative Analysis of Droplet-Based Ultra-High-Throughput Single-Cell RNA-Seq Systems.. Mol Cell 2019 Jan 3;73(1):130-142.e5.
- Grillo G, Turi A, Licciulli F, Mignone F, Liuni S, Banfi S, Gennarino VA, Horner DS, Pavesi G, Picardi E, Pesole G. UTRdb and UTRsite (RELEASE 2010): a collection of sequences and regulatory motifs of the untranslated regions of eukaryotic mRNAs.. Nucleic Acids Res 2010 Jan;38(Database issue):D75-80.
- Derr A, Yang C, Zilionis R, Sergushichev A, Blodgett DM, Redick S, Bortell R, Luban J, Harlan DM, Kadener S, Greiner DL, Klein A, Artyomov MN, Garber M. End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.. Genome Res 2016 Oct;26(10):1397-1410.
- Kabithe E, Hillegas J, Stokol T, Moore J, Wagner B. Monoclonal antibodies to equine CD14.. Vet Immunol Immunopathol 2010 Nov 15;138(1-2):149-53.
- Jakubzick CV, Randolph GJ, Henson PM. Monocyte differentiation and antigen-presenting functions.. Nat Rev Immunol 2017 Jun;17(6):349-362.
- Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, Punt JA, Geissmann F, Hedrick CC. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes.. Nat Immunol 2011 Jul 3;12(8):778-85.
- Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties.. Immunity 2003 Jul;19(1):71-82.
- Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, Puel A, Biswas SK, Moshous D, Picard C, Jais JP, D'Cruz D, Casanova JL, Trouillet C, Geissmann F. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors.. Immunity 2010 Sep 24;33(3):375-86.
- Gamrekelashvili J, Giagnorio R, Jussofie J, Soehnlein O, Duchene J, Briseño CG, Ramasamy SK, Krishnasamy K, Limbourg A, Kapanadze T, Ishifune C, Hinkel R, Radtke F, Strobl LJ, Zimber-Strobl U, Napp LC, Bauersachs J, Haller H, Yasutomo K, Kupatt C, Murphy KM, Adams RH, Weber C, Limbourg FP. Regulation of monocyte cell fate by blood vessels mediated by Notch signalling.. Nat Commun 2016 Aug 31;7:12597.
- Collin M, Bigley V. Human dendritic cell subsets: an update.. Immunology 2018 May;154(1):3-20.
- Caminschi I, Proietto AI, Ahmet F, Kitsoulis S, Shin Teh J, Lo JC, Rizzitelli A, Wu L, Vremec D, van Dommelen SL, Campbell IK, Maraskovsky E, Braley H, Davey GM, Mottram P, van de Velde N, Jensen K, Lew AM, Wright MD, Heath WR, Shortman K, Lahoud MH. The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement.. Blood 2008 Oct 15;112(8):3264-73.
- Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM. Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity.. Science 2008 Nov 14;322(5904):1097-100.
- Izaguirre A, Barnes BJ, Amrute S, Yeow WS, Megjugorac N, Dai J, Feng D, Chung E, Pitha PM, Fitzgerald-Bocarsly P. Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells.. J Leukoc Biol 2003 Dec;74(6):1125-38.
- Cisse B, Caton ML, Lehner M, Maeda T, Scheu S, Locksley R, Holmberg D, Zweier C, den Hollander NS, Kant SG, Holter W, Rauch A, Zhuang Y, Reizis B. Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.. Cell 2008 Oct 3;135(1):37-48.
- Wang Y, Bhattacharya D. Adjuvant-specific regulation of long-term antibody responses by ZBTB20.. J Exp Med 2014 May 5;211(5):841-56.
- Rubtsova K, Rubtsov AV, van Dyk LF, Kappler JW, Marrack P. T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance.. Proc Natl Acad Sci U S A 2013 Aug 20;110(34):E3216-24.
- Ehrhardt GR, Hsu JT, Gartland L, Leu CM, Zhang S, Davis RS, Cooper MD. Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells.. J Exp Med 2005 Sep 19;202(6):783-91.
- Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack P. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c⁺ B-cell population is important for the development of autoimmunity.. Blood 2011 Aug 4;118(5):1305-15.
- Rubtsova K, Rubtsov AV, Cancro MP, Marrack P. Age-Associated B Cells: A T-bet-Dependent Effector with Roles in Protective and Pathogenic Immunity.. J Immunol 2015 Sep 1;195(5):1933-7.
- Liu Y, Bezverbnaya K, Zhao T, Parsons MJ, Shi M, Treanor B, Ehrhardt GR. Involvement of the HCK and FGR src-family kinases in FCRL4-mediated immune regulation.. J Immunol 2015 Jun 15;194(12):5851-60.
- Karnell JL, Kumar V, Wang J, Wang S, Voynova E, Ettinger R. Role of CD11c(+) T-bet(+) B cells in human health and disease.. Cell Immunol 2017 Nov;321:40-45.
- Knox JJ, Buggert M, Kardava L, Seaton KE, Eller MA, Canaday DH, Robb ML, Ostrowski MA, Deeks SG, Slifka MK, Tomaras GD, Moir S, Moody MA, Betts MR. T-bet+ B cells are induced by human viral infections and dominate the HIV gp140 response.. JCI Insight 2017 Apr 20;2(8).
- Hedges JF, Graff JC, Jutila MA. Transcriptional profiling of gamma delta T cells.. J Immunol 2003 Nov 15;171(10):4959-64.
- Bezman NA, Kim CC, Sun JC, Min-Oo G, Hendricks DW, Kamimura Y, Best JA, Goldrath AW, Lanier LL. Molecular definition of the identity and activation of natural killer cells.. Nat Immunol 2012 Oct;13(10):1000-9.
- Schmiedel BJ, Singh D, Madrigal A, Valdovino-Gonzalez AG, White BM, Zapardiel-Gonzalo J, Ha B, Altay G, Greenbaum JA, McVicker G, Seumois G, Rao A, Kronenberg M, Peters B, Vijayanand P. Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression.. Cell 2018 Nov 29;175(6):1701-1715.e16.
- Zhao Y, Li X, Zhao W, Wang J, Yu J, Wan Z, Gao K, Yi G, Wang X, Fan B, Wu Q, Chen B, Xie F, Wu J, Zhang W, Chen F, Yang H, Wang J, Xu X, Li B, Liu S, Hou Y, Liu X. Single-cell transcriptomic landscape of nucleated cells in umbilical cord blood.. Gigascience 2019 May 1;8(5).
- Franzén O, Gan LM, Björkegren JLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data.. Database (Oxford) 2019 Jan 1;2019.
- Stoeckle C, Gouttefangeas C, Hammer M, Weber E, Melms A, Tolosa E. Cathepsin W expressed exclusively in CD8+ T cells and NK cells, is secreted during target cell killing but is not essential for cytotoxicity in human CTLs.. Exp Hematol 2009 Feb;37(2):266-75.
- van Aalderen MC, van den Biggelaar M, Remmerswaal EBM, van Alphen FPJ, Meijer AB, Ten Berge IJM, van Lier RAW. Label-free Analysis of CD8(+) T Cell Subset Proteomes Supports a Progressive Differentiation Model of Human-Virus-Specific T Cells.. Cell Rep 2017 May 2;19(5):1068-1079.
- Post M, Cuapio A, Osl M, Lehmann D, Resch U, Davies DM, Bilban M, Schlechta B, Eppel W, Nathwani A, Stoiber D, Spanholtz J, Casanova E, Hofer E. The Transcription Factor ZNF683/HOBIT Regulates Human NK-Cell Development.. Front Immunol 2017;8:535.
- Tallmadge RL, Wang M, Sun Q, Felippe MJB. Transcriptome analysis of immune genes in peripheral blood mononuclear cells of young foals and adult horses.. PLoS One 2018;13(9):e0202646.
- Vieira Braga FA, Hertoghs KM, Kragten NA, Doody GM, Barnes NA, Remmerswaal EB, Hsiao CC, Moerland PD, Wouters D, Derks IA, van Stijn A, Demkes M, Hamann J, Eldering E, Nolte MA, Tooze RM, ten Berge IJ, van Gisbergen KP, van Lier RA. Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans.. Eur J Immunol 2015 Oct;45(10):2945-58.
- Lanier LL. Up on the tightrope: natural killer cell activation and inhibition.. Nat Immunol 2008 May;9(5):495-502.
- Naeim F. Atlas of hematopathology: morphology, immunophenotype, cytogenetics, and molecular approaches. 2. Waltham: Elsevier; 2018.
- Noronha LE, Harman RM, Wagner B, Antczak DF. Generation and characterization of monoclonal antibodies to equine CD16.. Vet Immunol Immunopathol 2012 Apr 15;146(2):135-42.
- Noronha LE, Harman RM, Wagner B, Antczak DF. Generation and characterization of monoclonal antibodies to equine NKp46.. Vet Immunol Immunopathol 2012 Jun 15;147(1-2):60-8.
- Lunn DP, McClure JT, Schobert CS, Holmes MA. Abnormal patterns of equine leucocyte differentiation antigen expression in severe combined immunodeficiency foals suggests the phenotype of normal equine natural killer cells.. Immunology 1995 Mar;84(3):495-9.
- Ziegler-Heitbrock L. Monocyte subsets in man and other species.. Cell Immunol 2014 May-Jun;289(1-2):135-9.
- Mildner A, Jung S. Development and function of dendritic cell subsets.. Immunity 2014 May 15;40(5):642-56.
- Cavatorta DJ, Erb HN, Flaminio MJ. Ex vivo generation of mature equine monocyte-derived dendritic cells.. Vet Immunol Immunopathol 2009 Oct 15;131(3-4):259-67.
- Lee Y, Kiupel M, Soboll Hussey G. Characterization of respiratory dendritic cells from equine lung tissues.. BMC Vet Res 2017 Nov 6;13(1):313.
- Mauel S, Steinbach F, Ludwig H. Monocyte-derived dendritic cells from horses differ from dendritic cells of humans and mice.. Immunology 2006 Apr;117(4):463-73.
- Ziegler A, Marti E, Summerfield A, Baumann A. Identification and characterization of equine blood plasmacytoid dendritic cells.. Dev Comp Immunol 2016 Dec;65:352-357.
- Barnett BE, Staupe RP, Odorizzi PM, Palko O, Tomov VT, Mahan AE, Gunn B, Chen D, Paley MA, Alter G, Reiner SL, Lauer GM, Teijaro JR, Wherry EJ. Cutting Edge: B Cell-Intrinsic T-bet Expression Is Required To Control Chronic Viral Infection.. J Immunol 2016 Aug 15;197(4):1017-22.
- Piovesan D, Tempany J, Di Pietro A, Baas I, Yiannis C, O'Donnell K, Chen Y, Peperzak V, Belz GT, Mackay CR, Smyth GK, Groom JR, Tarlinton DM, Good-Jacobson KL. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses.. Cell Rep 2017 Apr 18;19(3):461-470.
- Jenks SA, Cashman KS, Zumaquero E, Marigorta UM, Patel AV, Wang X, Tomar D, Woodruff MC, Simon Z, Bugrovsky R, Blalock EL, Scharer CD, Tipton CM, Wei C, Lim SS, Petri M, Niewold TB, Anolik JH, Gibson G, Lee FE, Boss JM, Lund FE, Sanz I. Distinct Effector B Cells Induced by Unregulated Toll-like Receptor 7 Contribute to Pathogenic Responses in Systemic Lupus Erythematosus.. Immunity 2018 Oct 16;49(4):725-739.e6.
- Wang S, Wang J, Kumar V, Karnell JL, Naiman B, Gross PS, Rahman S, Zerrouki K, Hanna R, Morehouse C, Holoweckyj N, Liu H, Manna Z, Goldbach-Mansky R, Hasni S, Siegel R, Sanjuan M, Streicher K, Cancro MP, Kolbeck R, Ettinger R. IL-21 drives expansion and plasma cell differentiation of autoreactive CD11c(hi)T-bet(+) B cells in SLE.. Nat Commun 2018 May 1;9(1):1758.
- Obeng-Adjei N, Portugal S, Holla P, Li S, Sohn H, Ambegaonkar A, Skinner J, Bowyer G, Doumbo OK, Traore B, Pierce SK, Crompton PD. Malaria-induced interferon-γ drives the expansion of Tbethi atypical memory B cells.. PLoS Pathog 2017 Sep;13(9):e1006576.
- Portugal S, Tipton CM, Sohn H, Kone Y, Wang J, Li S, Skinner J, Virtaneva K, Sturdevant DE, Porcella SF, Doumbo OK, Doumbo S, Kayentao K, Ongoiba A, Traore B, Sanz I, Pierce SK, Crompton PD. Malaria-associated atypical memory B cells exhibit markedly reduced B cell receptor signaling and effector function.. Elife 2015 May 8;4.
- Burton AR, Pallett LJ, McCoy LE, Suveizdyte K, Amin OE, Swadling L, Alberts E, Davidson BR, Kennedy PT, Gill US, Mauri C, Blair PA, Pelletier N, Maini MK. Circulating and intrahepatic antiviral B cells are defective in hepatitis B.. J Clin Invest 2018 Oct 1;128(10):4588-4603.
- Divers TJ, Gardner RB, Madigan JE, Witonsky SG, Bertone JJ, Swinebroad EL, Schutzer SE, Johnson AL. Borrelia burgdorferi Infection and Lyme Disease in North American Horses: A Consensus Statement.. J Vet Intern Med 2018 Mar;32(2):617-632.
- Reed SM, Furr M, Howe DK, Johnson AL, MacKay RJ, Morrow JK, Pusterla N, Witonsky S. Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention.. J Vet Intern Med 2016 Mar-Apr;30(2):491-502.
- Raza A, Qamar AG, Hayat K, Ashraf S, Williams AR. Anthelmintic resistance and novel control options in equine gastrointestinal nematodes.. Parasitology 2019 Apr;146(4):425-437.
- Aran D, Looney AP, Liu L, Wu E, Fong V, Hsu A, Chak S, Naikawadi RP, Wolters PJ, Abate AR, Butte AJ, Bhattacharya M. Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage.. Nat Immunol 2019 Feb;20(2):163-172.
- Tan Y, Cahan P. SingleCellNet: A Computational Tool to Classify Single Cell RNA-Seq Data Across Platforms and Across Species.. Cell Syst 2019 Aug 28;9(2):207-213.e2.
- Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species.. Nat Biotechnol 2018 Jun;36(5):411-420.
- Stuart T, Butler A, Hoffman P, Hafemeister C, Papalexi E, Mauck WM 3rd, Hao Y, Stoeckius M, Smibert P, Satija R. Comprehensive Integration of Single-Cell Data.. Cell 2019 Jun 13;177(7):1888-1902.e21.
- Welch JD, Kozareva V, Ferreira A, Vanderburg C, Martin C, Macosko EZ. Single-Cell Multi-omic Integration Compares and Contrasts Features of Brain Cell Identity.. Cell 2019 Jun 13;177(7):1873-1887.e17.
- Patel RS, Tomlinson JE, Divers TJ, Van de Walle G, Rosenberg BR. Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells. Supplementary Datasets. NCBI Gene Expression Omnibus 2020.
- Patel RS, Rosenberg BR. Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells. R code. GitHub 2020.
- Kalbfleisch TS, Rice ES, DePriest MS Jr, Walenz BP, Hestand MS, Vermeesch JR, O Connell BL, Fiddes IT, Vershinina AO, Saremi NF, Petersen JL, Finno CJ, Bellone RR, McCue ME, Brooks SA, Bailey E, Orlando L, Green RE, Miller DC, Antczak DF, MacLeod JN. Improved reference genome for the domestic horse increases assembly contiguity and composition.. Commun Biol 2018;1:197.
- Wagner B. Immunoglobulins and immunoglobulin genes of the horse.. Dev Comp Immunol 2006;30(1-2):155-64.
- Gayoso A, Shor J. GitHub: DoubletDetection. Zenodo 2019.
- Hafemeister C, Satija R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression.. Genome Biol 2019 Dec 23;20(1):296.
- Waltman L, van Eck NJ. A smart local moving algorithm for large-scale modularity-based community detection. Eur Phys J B 2013;86:471.
- McInnes L, Healy J, Saul N, Großberger L. UMAP: uniform manifold approximation and projection. JOSS 2018;3:861.
- Zappia L, Oshlack A. Clustering trees: a visualization for evaluating clusterings at multiple resolutions.. Gigascience 2018 Jul 1;7(7).
- McCarthy DJ, Chen Y, Smyth GK. Differential expression analysis of multifactor RNA-Seq experiments with respect to biological variation.. Nucleic Acids Res 2012 May;40(10):4288-97.
- Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.. Bioinformatics 2010 Jan 1;26(1):139-40.
- Soneson C, Robinson MD. Bias, robustness and scalability in single-cell differential expression analysis.. Nat Methods 2018 Apr;15(4):255-261.
- Bausch-Fluck D, Hofmann A, Bock T, Frei AP, Cerciello F, Jacobs A, Moest H, Omasits U, Gundry RL, Yoon C, Schiess R, Schmidt A, Mirkowska P, Härtlová A, Van Eyk JE, Bourquin JP, Aebersold R, Boheler KR, Zandstra P, Wollscheid B. A mass spectrometric-derived cell surface protein atlas.. PLoS One 2015;10(3):e0121314.
- Zilionis R, Engblom C, Pfirschke C, Savova V, Zemmour D, Saatcioglu HD, Krishnan I, Maroni G, Meyerovitz CV, Kerwin CM, Choi S, Richards WG, De Rienzo A, Tenen DG, Bueno R, Levantini E, Pittet MJ, Klein AM. Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species.. Immunity 2019 May 21;50(5):1317-1334.e10.
- Ward JH. Hierarchical grouping to optimize an objective function. J Am Stat Assoc 1963;58:236–244.
- Blanchard-Channell M, Moore PF, Stott JL. Characterization of monoclonal antibodies specific for equine homologues of CD3 and CD5.. Immunology 1994 Aug;82(4):548-54.
- Lunn DP, Holmes MA, Antczak DF, Agerwal N, Baker J, Bendali-Ahcene S, Blanchard-Channell M, Byrne KM, Cannizzo K, Davis W, Hamilton MJ, Hannant D, Kondo T, Kydd JH, Monier MC, Moore PF, O'Neil T, Schram BR, Sheoran A, Stott JL, Sugiura T, Vagnoni KE. Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.. Vet Immunol Immunopathol 1998 Mar 31;62(2):101-43.
- Lunn DP, Holmes MA, Duffus WP. Three monoclonal antibodies identifying antigens on all equine T lymphocytes, and two mutually exclusive T-lymphocyte subsets.. Immunology 1991 Oct;74(2):251-7.
- Ibrahim S, Steinbach F. Non-HLDA8 animal homologue section anti-leukocyte mAbs tested for reactivity with equine leukocytes.. Vet Immunol Immunopathol 2007 Sep 15;119(1-2):81-91.
- Ibrahim S, Steinbach F. Immunoprecipitation of equine CD molecules using anti-human MABs previously analyzed by flow cytometry and immunohistochemistry.. Vet Immunol Immunopathol 2012 Jan 15;145(1-2):7-13.
- Wagner B, Hillegas JM, Babasyan S. Monoclonal antibodies to equine CD23 identify the low-affinity receptor for IgE on subpopulations of IgM+ and IgG1+ B-cells in horses.. Vet Immunol Immunopathol 2012 Apr 15;146(2):125-34.
- Wagner B, Glaser A, Hillegas JM, Erb H, Gold C, Freer H. Monoclonal antibodies to equine IgM improve the sensitivity of West Nile virus-specific IgM detection in horses.. Vet Immunol Immunopathol 2008 Mar 15;122(1-2):46-56.
Citations
This article has been cited 9 times.- Eschke M, Moore PF, Chang H, Alber G, Keller SM. Canine peripheral blood TCRαβ T cell atlas: Identification of diverse subsets including CD8A(+) MAIT-like cells by combined single-cell transcriptome and V(D)J repertoire analysis.. Front Immunol 2023;14:1123366.
- Zhang C, Wang N, Chen G, Tang G, Tam C, Tan HY, Xu X, Feng Y. Single-cell co-expression analysis using computational machine learning reveals oxidative, immunopathologic, and myocardial responses for multi-organ failure in COVID-19.. Clin Transl Med 2022 Oct;12(10):e1049.
- Sage SE, Nicholson P, Peters LM, Leeb T, Jagannathan V, Gerber V. Single-cell gene expression analysis of cryopreserved equine bronchoalveolar cells.. Front Immunol 2022;13:929922.
- Harman RM, Churchill KA, Parmar S, Van de Walle GR. Mesenchymal stromal cells isolated from chicken peripheral blood secrete bioactive factors with antimicrobial and regenerative properties.. Front Vet Sci 2022;9:949836.
- Gao X, Cockburn IA. The development and function of CD11c(+) atypical B cells - insights from single cell analysis.. Front Immunol 2022;13:979060.
- Wiarda JE, Trachsel JM, Sivasankaran SK, Tuggle CK, Loving CL. Intestinal single-cell atlas reveals novel lymphocytes in pigs with similarities to human cells.. Life Sci Alliance 2022 Oct;5(10).
- Gressler AE, Lübke S, Wagner B, Arnold C, Lohmann KL, Schnabel CL. Comprehensive Flow Cytometric Characterization of Bronchoalveolar Lavage Cells Indicates Comparable Phenotypes Between Asthmatic and Healthy Horses But Functional Lymphocyte Differences.. Front Immunol 2022;13:896255.
- Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR, Rice CM, Divers TJ, Van de Walle GR, Scheel TKH. Pathogenesis, MicroRNA-122 Gene-Regulation, and Protective Immune Responses After Acute Equine Hepacivirus Infection.. Hepatology 2021 Sep;74(3):1148-1163.
- Hagen A, Lehmann H, Aurich S, Bauer N, Melzer M, Moellerberndt J, Patané V, Schnabel CL, Burk J. Scalable Production of Equine Platelet Lysate for Multipotent Mesenchymal Stromal Cell Culture.. Front Bioeng Biotechnol 2020;8:613621.
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