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Webinar
Combination of single-cell transcriptomics and multi-parameter flow cytometry to better understand cellular heterogeneity and function in humans
Jonas Schulte-Schrepping, Lorenzo Bonaguro, Marc Beyer
Chair: Anja Hauser, DGfZ
German Center for Neurodegenerative Diseases (DZNE), Bonn
Recent technical advances in the fields of flow cytometry and single-cell Omics have greatly increased our understanding of cellular heterogeneity and paved the way for initiatives charting the cells of the immune system and the human body.
We have set out to harness these new technologies to characterize the cellular heterogeneity in the CNS as well as the human immune system in chronic and acute infections and its influence during the development and progression of neurodegenerative diseases.
By combining multi-parameter flow cytometry with single-cell transcriptomics we could recently fine-map the human blood-borne immune response to COVID-19 infections and describe the occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, as well as dysfunctional mature neutrophils as a hallmark of severe COVID-19 infections.
Taken together, these data clearly demonstrate the usefulness of this approach to address questions focusing on cellular differentiation processes as well as ontogeny and function, which so far could not be sufficiently answered.
Speaker: Marc Beyer
Home Institution:
Deutsches Zentrum für Neurodegenerative Erkrankungen e. V. (DZNE)
German Center for Neurodegenerative Diseases
Group leader for Molekulare Immunologie & Neurodegeneration
About his research focus:
The group of Dr. Beyer is highly interested in unraveling the molecular events in innate and adaptive immune cells resulting in their activation and functional reprogramming contributing to the development of neurodegenerative disorders.
One main research focus is the characterization of regulatory T cells, T cell differentiation and T cell exhaustion. Seminal work of the group could show the importance of the chromatin remodeler special AT-rich binding protein 1 (Satb1) for the function of Treg cells and peripheral T cells and its influence on the development of autoimmunity. Furthermore, the group could show that chronic exposure to the proinflammatory cytokine TNF can be causative for T cells dysfunction in chronic viral infections. Following up on these observations, the group is currently assessing the importance of T cells for CNS pathology.
Links
Key Publications
Schmidleithner L, Thabet Y, Schönfeld E, Köhne M, Sommer D, Abdullah Z, Sadlon T, Osei-Sarpong C, Subbaramaiah K, Copperi F, Haendler K, Varga T, Schanz O, Bourry S, Bassler K, Krebs W, Peters AE, Baumgart AK, Schneeweiss M, Klee K, Schmidt SV, Nüssing S, Sander J, Ohkura N, Waha A, Sparwasser T, Wunderlich FT, Förster I, Ulas T, Weighardt H, Sakaguchi S, Pfeifer A, Blüher M, Dannenberg AJ, Ferreirós N, Muglia LJ, Wickenhauser C, Barry SC, Schultze JL, Beyer M. Enzymatic Activity of HPGD in Treg Cells Suppresses Tconv Cells to Maintain Adipose Tissue Homeostasis and Prevent Metabolic Dysfunction. Immunity. 2019 May 25; 50:1232-1248. doi: 10.1016/j.immuni.2019.03.014
Mass E,Ballesteros I, Farlik M, Halbritter F, Günther P, Crozet L, Jacome-Galarza CE, Händler K, Klughammer J, Kobayashi Y, Gomez-Perdiguero E, Schultze JL, Beyer M, Bock C*, Geissmann F. Differentiation and specification of tissue-resident macrophages. Science. 2016 Sep 09; 353:6304. doi: 10.1126/science.aaf4238
Beyer M, Abdullah Z, Chemnitz JM, Maisel D, Shinde PV, Lehmann C, Thabet Y, Hofmann A, Popov A, Lang KS, Fätkenheuer G, Lang PA, Hartmann P, Knolle PA, Schultze JL. TNF dependent induction of inhibitory pathways in CD4+ T cells in advanced human HIV and murine LCMV infection. Nat Immunol. 2016 Mar 07; doi: 10.1038/ni.3399
Sommer D, Peters A, Wirtz T, Mai M, Ackermann J, Thabet Y, Schmidt J, Weighardt H, Wunderlich FT, Degen J, Schultze JL, Beyer M. Efficient genome engineering by targeted homologous recombination in mouse embryos using transcription activator-like effector nucleases. Nat Commun. 2014 Jan 13; 5:3045. doi: 10.1038/ncomms4045
Beyer M, Thabet Y, Müller RU, Sadlon T, Classen S, Lahl K, Basu S, Zhou X, Bailey-Bucktrout SL, Krebs W, Schönfeld EA, Böttcher J, Golovina T, Mayer CT, Hofmann A, Sommer D, Debey-Pascher S, Endl E, Limmer A, Hippen KL, Blazar BR, Balderas R, Quast T, Waha A, Mayer G, Famulok M, Knolle PA, Wickenhauser C, Kolanus W, Schermer B, Bluestone JA, Barry SC, Sparwasser T, Riley JL, Schultze JL. Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation. Nat Immunol. 2011 Aug 14; 12:898-907.