DUDLI-LAB
Newest Publication
Massively parallel flow-cytometry-based screening of hematopoietic lineage cell populations from up to 25 donors simultaneously
Abstract
This study aimed to develop a method allowing high-dimensional and technically uniform screening of surface markers on cells of hematopoietic origin. High-dimensional screening of cell phenotypes is primarily the domain of single-cell RNA sequencing (RNAseq), which allows simultaneous analysis of the expression of thousands of genes in several thousands of cells. However, rare cell populations can often substantially impact tissue homeostasis or disease pathogenesis, and dysregulation of rare populations can easily be missed when only a few thousand cells are analyzed. With the presented methodological approach it is possible to screen hundreds of markers on millions of cells in a technically uniform manner and thus identify and characterize changes in rare populations.
We utilize the highly expressed markers CD45 on immune cells and CD71 on erythroid progenitors to create unique fluorescent barcodes on each of the 25 samples. Double-barcoded samples are co-stained with a broad immunophenotyping panel. The panel is designed in such a way that allows the addition of PE-labelled antibody, which was used for screening purposes. Multiplexed samples are divided into hundreds of aliquots and co-stained, each aliquot with a different PE-labelled antibody. Utilizing a broad immunophenotyping panel and machine-learning algorithms, we can predict the co-expression of hundreds of screened markers with a high degree of precision. This technique is suitable for screening immune cells in bone marrow from different locations, blood specimens, or any tissue with a substantial presence of immune cells, such as tumors or inflamed tissue areas in autoimmune conditions. It represents an approach that can significantly improve our ability to recognize dysregulated immune cell populations and, if needed, precisely target subsequent experiments covering lower cell counts such as RNAseq.
All Publications
The Expression of Toll-like Receptors in Cartilage Endplate Cells: A Role of Toll-like Receptor 2 in Pro-Inflammatory and Pro-Catabolic Gene Expression
Mengis, T., Bernhard, L., Nüesch, A., Heggli, I., Herger, N., Devan, J., Marcus, R., Laux, C. J., Brunner, F., Farshad, M., Distler, O., Le Maitre, C. L., & Dudli, S. (2024). The Expression of Toll-like Receptors in Cartilage Endplate Cells: A Role of Toll-like Receptor 2 in Pro-Inflammatory and Pro-Catabolic Gene Expression. Cells, 13(17), 1402. https://doi.org/10.3390/cells13171402
Intervertebral disc microbiome in Modic changes: Lack of result replication underscores the need for a consensus in low-biomass microbiome analysis
Mengis T, Zajac N, Bernhard L, Heggli I, Herger N, Devan J, Marcus R, Brunner F, Laux C, Farshad M, Distler O, Dudli S. Intervertebral disc microbiome in Modic changes: Lack of result replication underscores the need for a consensus in low-biomass microbiome analysis. JOR Spine. 2024 Apr 4;7(2):e1330. doi: 10.1002/jsp2.1330. PMID: 38585427; PMCID: PMC10995447.
Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes
Schulze F, Määttä J, Grad S, Heggli I, Brunner F, Farshad M, Distler O, Karppinen J, Lotz J, Dudli S. Proteomic analysis of serum in a population-based cohort did not reveal a biomarker for Modic changes. JOR Spine. 2024 Jul 15;7(3):e1337. doi: 10.1002/jsp2.1337. PMID: 39015135; PMCID: PMC11250394.
Impacts of priming on distinct immunosuppressive mechanisms of mesenchymal stromal cells under translationally relevant conditions
Herger N, Heggli I, Mengis T, Devan J, Arpesella L, Brunner F, Distler O, Dudli S. Impacts of priming on distinct immunosuppressive mechanisms of mesenchymal stromal cells under translationally relevant conditions. Stem Cell Res Ther. 2024 Mar 5;15(1):65. doi: 10.1186/s13287-024-03677-5. PMID: 38443999; PMCID: PMC10916130.
Low back pain patients with Modic type 1 changes exhibit distinct bacterial and non-bacterial subtypes
I. Heggli, T. Mengis, C.J. Laux, L. Opitz, N. Herger, D. Menghini, R. Schuepbach, N.A. Farshad Amacker , F. Brunner, A.J. Fields, M. Farshad, O. Distler, S. Dudli
Osteoarthr Cartil Open. 2024;6(1):100434. Published 2024 Jan 18. doi:10.1016/j.ocarto.2024.100434
https://www.sciencedirect.com/science/article/pii/S2665913124000013
The role of the complement system in disc degeneration and Modic changes
Irina Heggli, Graciosa Q. Teixeira, James C. Iatridis, Cornelia Neidlinger‐Wilke and Stefan Dudli
JOR Spine. 2024 Mar; 7(1): e1312. Published online 2024 Feb 2. doi: 10.1002/jsp2.1312
Bone marrow stromal cells in Modic type 1 changes promote neurite outgrowth
Mengis T, Herger N, Heggli I, Devan J, Spirig JM, Laux CJ, Brunner F, Farshad M, Distler O, Dudli S.
Front Cell Dev Biol. 2023 Oct 25;11:1286280. doi: 10.3389/fcell.2023.1286280. eCollection 2023. PMID: 37965581
https://www.frontiersin.org/articles/10.3389/fcell.2023.1286280/full
Cartilaginous endplates: A comprehensive review on a neglected structure in intervertebral disc research
Crump KB, Alminnawi A, Bermudez-Lekerika P, Compte R, Gualdi F, McSweeney T, Muñoz-Moya E, Nüesch A, Geris L, Dudli S, Karppinen J, Noailly J, Le Maitre C, Gantenbein B.
JOR Spine. 2023 Oct 21. DOI: 10.1002/jsp2.1294. eCollection 2023 Dec.
Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates
Irina Heggli, Christoph J. Laux, Tamara Mengis, Agnieszka Karol, Frédéric Cornaz, Nick Herger, Borbala Aradi‐Vegh, Jonas Widmer, Marco D. Burkhard, Nadja A. Farshad‐Amacker, Sibylle Pfammatter, Witold E. Wolski, Florian Brunner, Oliver Distler, Mazda Farshad, and Stefan Dudli
JOR spine, 2023. DOI: 10.1002/jsp2.1237
The role of the bone in complex regional pain syndrome 1-A systematic review
Gil Kollmann, Maria M Wertli, Stefan Dudli, Oliver Distler, Florian Brunner
Eur J Pain. 2023 Mar 31. DOI: 10.1002/ejp.2116. Online ahead of print.
Harmonization and Standardization of Nucleus pulposus Cell Culture Methods.
Basatvat S, Binch ALA, Snuggs J, Owen D, Williams R, Richardson SM, Hoyland JA, Gansau J, Buckley CT, Glaeser JD, Sheyn D, Wang D, Vo N , Jacobsen T, Chahine NO, Presciutti SM, Drissi H, Yoon T, Illien-Junger S, Gawri R, Lang G, Hernandez PA, Fearing BV, Setton LA, Dudli S, Schol J, Sakai D, Guerrero J, Gantenbein B, Li Z, Peroglio M, Grad S, Kraus P, Lufkin T, O'Connell GD, Dahia C, Kaito T, Kushioka J, Wachs RA, DiStefano T, Panebianco C, Iatridis JC, Bowles RD, Sun Y, Leung VY, Haglund L, Mizuno S, Huang CY, Alvarez-Garcia O, Silverman L, Li X, Garcia JP, Creemers LB, Ito K, Medzikovic A, van Maanen JC, Laagland LT, Bach FC, Tryfonidou MA, L. Le Maitre C.
JOR Spine. e1238, DOI: 10.1002/jsp2.1238
FGF2 overrides key pro-fibrotic features of bone marrow stromal cells isolated from Modic type 1 change patients
I Heggli, U Blache, N Herger, T Mengis, PK Jaeger, R Schuepbach, N Farshad-Amacker, F Brunner, JG Snedeker, M Farshad, O Distler, S Dudli
European Cells and Materials Vol. 44 2022 (pages 101-114) DOI: 10.22203/eCM.v044a07
Protocol for Biospecimen Collection and Analysis within the BACPAC Research Program.
Fields AJ, Dudli S, Schrepf A, Kim A, Pham B, Gallego E, Mendoza S, Meropol SB, Darwin J, Sowa G, Vo NV.
Pain Med. 2022 Dec 16:pnac197. doi: 10.1093/pm/pnac197. Online ahead of print.
PMID: 36525387
Role of C-reactive protein in the bone marrow of Modic type 1 changes.
Dudli S, Heggli I, Laux CJ, Spirig JM, Wanivenhaus F, Betz M, Germann C, Farshad-Amacker NA, Herger N, Mengis T, Brunner F, Farshad M, Distler O.J Orthop Res. 2022
Sep 5. doi: 10.1002/jor.25437. Online ahead of print.
PMID: 36062874
CD90-positive stromal cells associate with inflammatory and fibrotic changes in modic changes.
Dudli S, Karol A, Giudici L, Heggli I, Laux CJ, Spirig JM, Wanivenhaus F, Betz M, Germann C, Farshad-Amacker N, Brunner F, Distler O, Farshad M.Osteoarthr Cartil Open. 2022 Jun 22;4(3):100287. doi: 10.1016/j.ocarto.2022.100287. eCollection 2022 Sep.
PMID: 36474945
Intervertebral disc cell chondroptosis elicits neutrophil response in Staphylococcus aureus spondylodiscitis.
Schweizer TA, Andreoni F, Acevedo C, Scheier TC, Heggli I, Maggio EM, Eberhard N, Brugger SD, Dudli S, Zinkernagel AS.
Front Immunol. 2022 Jul 28;13:908211. doi: 10.3389/fimmu.2022.908211. eCollection 2022.
PMID: 35967370
Should Degenerated Intervertebral Discs of Patients with Modic Type 1 Changes Be Treated with Mesenchymal Stem Cells?
Herger N, Bermudez-Lekerika P, Farshad M, Albers CE, Distler O, Gantenbein B, Dudli S.
Int J Mol Sci. 2022 Feb 28;23(5):2721. doi: 10.3390/ijms23052721.
PMID: 35269863
Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section.
Lai A, Gansau J, Gullbrand SE, Crowley J, Cunha C, Dudli S, Engiles JB, Fusellier M, Goncalves RM, Nakashima D, Okewunmi J, Pelletier M, Presciutti SM, Schol J, Takeoka Y, Yang S, Yurube T, Zhang Y, Iatridis JC.
JOR Spine. 2021 May 26;4(2):e1150. doi: 10.1002/jsp2.1150. eCollection 2021 Jun.
PMID: 34337335
Karppinen J, Koivisto K, Ketola J, Haapea M, Paananen M, Herzig KH, Alini M, Lotz J, Dudli S, Samartzis D, Risteli J, Majuri ML, Alenius H, Kyllönen E, Järvinen J, Niinimäki J, Grad S.
Eur Spine J. 2021 Apr;30(4):1018-1027. doi: 10.1007/s00586-020-06713-z. Epub 2021 Jan 9.
PMID: 33423134
Pro-Inflammatory and Neurotrophic Factor Responses of Cells Derived from Degenerative Human Intervertebral Discs to the Opportunistic Pathogen Cutibacterium acnes
Capoor MN, Konieczna A, McDowell A, Ruzicka F, Smrcka M, Jancalek R, Maca K, Lujc M, Ahmed FS, Birkenmaier C, Dudli S, Slaby O.
Int J Mol Sci. 2021 Feb 26;22(5):2347. doi: 10.3390/ijms22052347.
PMID: 33652921
Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes).
Dudli S, Ballatori A, Bay-Jensen AC, McCormick ZL, O'Neill CW, Demir-Deviren S, Krug R, Heggli I, Juengel A, Karppinen J, Brunner F, Farshad M, Distler O, Lotz JC, Fields AJ.
Int J Mol Sci. 2020 May 27;21(11):3791. doi: 10.3390/ijms21113791.
PMID: 32471173
The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging.
Koivisto K, Karppinen J, Haapea M, Järvinen J, Kyllönen E, Tervonen O, Niinimäki J, Alini M, Lotz J, Dudli S, Samartzis D, Risteli J, Majuri ML, Alenius H, Grad S.
Diagnostics (Basel). 2019 Dec 4;9(4):212. doi: 10.3390/diagnostics9040212.
PMID: 31817123
Pulsed electromagnetic fields reduce acute inflammation in the injured rat-tail intervertebral disc.
Chan AK, Tang X, Mummaneni NV, Coughlin D, Liebenberg E, Ouyang A, Dudli S, Lauricella M, Zhang N, Waldorff EI, Ryaby JT, Lotz JC.
JOR Spine. 2019 Dec 2;2(4):e1069. doi: 10.1002/jsp2.1069. eCollection 2019 Dec.
PMID: 31891118
Quantification of Propionic Acid in the Bovine Spinal Disk After Infection of the Tissue With Propionibacteria acnes Bacteria.
Magnitsky S, Dudli S, Tang X, Kaur J, Diaz J, Miller S, Lotz JC.
Spine (Phila Pa 1976). 2018 Jun 1;43(11):E634-E638. doi: 10.1097/BRS.0000000000002448.
PMID: 29019804
Modic type 1 change is an autoimmune response that requires a proinflammatory milieu provided by the 'Modic disc'.
Dudli S, Liebenberg E, Magnitsky S, Lu B, Lauricella M, Lotz JC.
Spine J. 2018 May;18(5):831-844. doi: 10.1016/j.spinee.2017.12.004. Epub 2017 Dec 15.
PMID: 29253635
Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes.
Dudli S, Miller S, Demir-Deviren S, Lotz JC.
Eur Spine J. 2018 May;27(5):1013-1020. doi: 10.1007/s00586-017-5291-4. Epub 2017 Sep 7.
PMID: 28884220
Machine Learning-Based Classification of 38 Years of Spine-Related Literature Into 100 Research Topics.
Sing DC, Metz LN, Dudli S.
Spine (Phila Pa 1976). 2017 Jun 1;42(11):863-870. doi: 10.1097/BRS.0000000000002079.
PMID: 28125523
ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes.
Dudli S, Sing DC, Hu SS, Berven SH, Burch S, Deviren V, Cheng I, Tay BKB, Alamin TF, Ith MAM, Pietras EM, Lotz JC.
Eur Spine J. 2017 May;26(5):1362-1373. doi: 10.1007/s00586-017-4955-4. Epub 2017 Jan 31.
PMID: 28138783
Dudli S, Fields AJ, Samartzis D, Karppinen J, Lotz JC.
Eur Spine J. 2016 Nov;25(11):3723-3734. doi: 10.1007/s00586-016-4459-7. Epub 2016 Feb 25.
PMID: 26914098
Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes.
Dudli S, Liebenberg E, Magnitsky S, Miller S, Demir-Deviren S, Lotz JC.
J Orthop Res. 2016 Aug;34(8):1447-55. doi: 10.1002/jor.23265. Epub 2016 Aug 3.
PMID: 27101067
Dudli S, Ferguson SJ, Haschtmann D.
Spine J. 2014 Jul 1;14(7):1256-64. doi: 10.1016/j.spinee.2013.07.488. Epub 2014 Feb 28.
PMID: 24583791