tapio.lonnberg [at] utu.fi
Single-Cell Immunogenomics Group
BioCity, Tykistökatu 6
20520 Turku, Finland
+358 (0)29 450 3738
About our research
Our research aims at gaining deeper understanding of cell fate decisions in the immune system by leveraging single cell sequencing. In particular, our research focuses on T cells and other lymphoid cells, and addresses how their functional diversity is shaped in health and disease. With the use of single-cell approaches, we aim to see beyond the canonical immune cell subsets defined by the expression of cell surface markers. By exploring the core gene modules that are selectively activated or repressed in response to extracellular signals, we try to elucidate the regulatory processes leading to distinct cellular phenotypes that ultimately determine the outcome of an immune response.
Reprogramming of macrophage phenotypes as an early predictor of cardiovascular and metabolic disease development
Macrophages represent a key cell type that surveil all tissues in the body for signs of damage and danger from foreign pathogens. However, they are not passive observers. Within each tissue, macrophages play a central role in altering the phenotype of other tissue-resident cells such as fuelling adipose tissue inflammation in obesity that can distally promote inflammation in the vascular wall via secreted cytokines to promote coronary artery disease. Reciprocally, the tissue environments can shape a remarkable diversity of macrophage phenotypes. Nonetheless, our collective understanding of the contribution of these different tissue-specific macrophages in disease etiology remains in its infancy. By single cell sequencing of key immune cell populations from affected and peripheral tissues, we aim to find early disease biomarkers. The work is part of a research consortium led by Prof. Merja Heinäniemi and funded by the Academy of Finland Health from Science Academy Programme.
Atlas of T cells in Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is a debilitating systemic autoimmune disease affecting about 1% of the population. Despite intense research, many key aspects of the disease remain elusive, including the mechanisms by which inflammation is caused and sustained in the joints. While abundant T cells have been detected in the inflamed synovial tissue, their phenotypes and mechanisms of differentiation are poorly understood. Our goal is to elucidate the functional diversity of activated T cells in RA patients, focusing especially on those cells that interact with B cells, thus potentially playing a role in the generation of autoantibodies. By using single-cell approaches, we aim to identify the T cell subpopulations that are specifically associated with the disease, potentially revealing targets for therapeutic interventions.
Örd T, Õunap K, Stolze LK, Aherrahrou R, Nurminen V, Toropainen A, Selvarajan I, Lönnberg T, Aavik E, Ylä-Herttuala S, Civelek M, Romanoski CE, Kaikkonen MU:
Single-Cell Epigenomics and Functional Fine-Mapping of Atherosclerosis GWAS Loci.
Circulation Research 2021 129(2):240-258. PMID: 34024118
Oliva-Olivera W, Castellano-Castillo D, von Meyenn F, Cardona F, Lönnberg T *& Tinahones FJ*:
Human adipose tissue-derived stem cell paracrine networks vary according metabolic risk and after TNFα-induced death: an analysis at the single-cell level.
Metabolism 2021; 116:154466. PMID: 33333081
*) Equal contribution
Kelkka T, Savola P, Bhattacharya D, Huuhtanen J, Lönnberg T, Kankainen M, Paalanen K, Tyster M, Lepistö M, Ellonen P, Smolander J, Eldfors S, Yadav B, Khan S, Koivuniemi R, Sjöwall C, Elo LL, Lähdesmäki H, Maeda Y, Nishikawa H, Leirisalo-Repo M, Sokka-Isler T, & Mustjoki S:
Adult-Onset Anti-Citrullinated Peptide Antibody-Negative Destructive Rheumatoid Arthritis Is Characterized by a Disease-Specific CD8+ T Lymphocyte Signature.
Frontiers in Immunology 2021; 12:710831. PMID: 34135915
Mehtonen J, Teppo S, Lahnalampi M, Kokko A, Kaukonen R, Oksa L, Bouvy-Liivrand M, Malyukova A, Mäkinen A, Laukkanen S, Mäkinen PI, Rounioja S, Ruusuvuori P, Sangfelt O, Lund R, Lönnberg T, Lohi O & Heinäniemi M:
Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities.
Genome Medicine 2020; 12(1):99. PMID: 33218352
Depuydt MAC, Prange KHM, Slenders L, Örd T, Elbersen D, Boltjes A, de Jager SCA, Asselbergs FW, de Borst GJ, Aavik E, Lönnberg T, Lutgens E, Glass CK, Kaikkonen MU, Bot I, Slütter B, van der Laan SW, Yla-Herttuala S, Mokry M, Kuiper J, de Winther MPJ & Pasterkamp G:
Microanatomy of the human atherosclerotic plaque by single-cell transcriptomics.
Circulation Research 2020 127(11):1437-1455. PMID: 32981416
Soon M, Lee HJ, Engel J, Straube J, Thomas B, Pernold C, Clarke L, Haldar R, Williams C, Lansink L, Kazakoff S, Koufariotis L, Wood S, Chen X, James K, Lönnberg T, Lane S, Belz G, Engwerda C, Khoury D, Davenport MP, Svensson V, Teichmann SA & Haque A:
Transcriptome Dynamics of CD4+ T cells during Malaria Maps Progressive Transition from Effector to Memory.
Nature Immunology 2020; 21(12):1597-1610. PMID: 33046889
Kim D*, Park G*, Huuhtanen J, Lundgren S, Khajuria RK, Hurtado AM, Muñoz-Calleja C, Cardeñoso L, Gómez-García de Soria V, Chen-Liang TH, Eldfors S, Ellonen P, Hannula S, Bruck O, Kreutzman A, Salmenniemi U, Lönnberg T, Jerez A, Itälä-Remes M, Myllymäki M, Keränen MAI & Mustjoki S:
Somatic Gain-of-Function mTOR mutation in Clonally Expanded T-lymphocytes Associated with Chronic Graft-Versus-Host Disease
Nature communications 2020; 11(1):2246. PMID: 32382059
*) Equal contribution
Takeda A, Hollmén M, Dermadi D, Pan J, Brulois KF, Kaukonen R, Lönnberg T, Boström P, Koskivuo I, Irjala H, Miyasaka M, Salmi M, Butcher EC & Jalkanen S:
Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.
Immunity 2019; 51(3):561-72. PMID: 31402260
Kallionpää H, Somani J, Tuomela S, Ullah U, de Albuquerque R, Lönnberg T, Komsi E, Siljander H, Honkanen J, Härkönen T, Peet A, Tillmann T, Chandra V, Anagandula MK, Frisk G, Otonkoski T, Rasool O, Lund R, Lähdesmäki H, Knip M & Lahesmaa R.
Early detection of peripheral blood cell signature in children developing beta-cell autoimmunity at a young age.
Diabetes 2019; 68(10), 2024-2034. PMID 31311800
Miragaia RJ, Zhang X, Gomes T, Svensson V, Ilicic T, Henriksson J, Kar G & Lönnberg T.
Single-cell RNA-sequencing resolves self-antigen expression during mTEC development.
Scientific Reports 2018; 8(1):685. PMID: 29330484
Haque A, Engel J, Teichmann SA & Lönnberg T:
A practical guide to single-cell RNA-sequencing for biomedical research and clinical applications.
Genome Medicine 2017; 9(1):75. Review. PMID:28821273
Kolodziejczyk AA* & Lönnberg T*:
Global and targeted approaches to single-cell transcriptome characterization.
Briefings in Functional Genomics 2017; Review. PMID:29028866
*) Equal contribution
Lönnberg T*, Svensson V*, James KR*, Fernandez-Ruiz D, Sebina I, Montandon R, Soon MSF, Fogg LG, Nair AS, Liligeto UN, Stubbington MJT, Ly LH, Bagger FO, Zwiessele M, Lawrence ND, Souza-Fonseca-Guimaraes F, Bunn PT, Engwerda CR, Heath WR, Billker O, Stegle O, Haque A, & Teichmann SA:
Single-cell RNA-seq and computational analysis using temporal mixture modelling resolves TH1/TFH fate bifurcation in malaria.
Science Immunology 2017; 2:1-11. PMID 28345074
*) Equal contribution
Proserpio V, Piccolo A, Haim-Vilmovsky L, Kar G, Lönnberg T, Svensson V, Pramanik J, Natarajan KN, Zhai W, Zhang, X, Donati G, Kayikci M, Kotar J, McKenzie ANJ, Montandon R, Billker O, Woodhouse S, Cicuta P, Nicodemi M & Teichmann SA:
Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation.
Genome Biology 2016; 17:103. PMID: 27176874
Proserpio V & Lönnberg T:
Single-cell technologies are revolutionizing the approach to rare cells.
Immunology and Cell Biology 2016; 94(3):225-9. Review. PMID: 26620630
Stubbington MJT*, Lönnberg T*, Proserpio V, Clare S, Speak AO, Dougan G & Teichmann SA:
T cell fate and clonality inference from single-cell transcriptomes.
Nature Methods 2016; 13(4):329-32. PMID: 26950746
*) Equal contribution
Hawkins RD, Larjo A, Tripathi SK, Wagner U, Luu Y, Lönnberg T, Raghav SK, Lee LK, Lund R, Ren B, Lähdesmäki H & Lahesmaa R:
Global chromatin state analysis reveals lineage-specific enhancers during the initiation of human T helper 1 and T helper 2 cell polarization.
Immunity 2013; 38(6):1271-84. PMID: 23791644
Chen Z, Lönnberg T & Lahesmaa R:
Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.
Scandinavian Journal of Immunology 2013; 78(2):172-80. Review. PMID: 23679154
Lönnberg T, Chen Z & Lahesmaa R:
From a gene-centric to whole-proteome view of differentiation of T helper cell subsets.
Briefings in Functional Genomics 2013; 12(6):471-82. Review. PMID: 24106101