LifeTime and improving European healthcare through cell-based interceptive medicine.
Journal
Nature
ISSN: 1476-4687
Titre abrégé: Nature
Pays: England
ID NLM: 0410462
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
29
04
2020
accepted:
25
08
2020
pubmed:
8
9
2020
medline:
18
2
2021
entrez:
7
9
2020
Statut:
ppublish
Résumé
Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
Identifiants
pubmed: 32894860
doi: 10.1038/s41586-020-2715-9
pii: 10.1038/s41586-020-2715-9
pmc: PMC7656507
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
377-386Investigateurs
Lavinia Alberi
(L)
Stephanie Alexander
(S)
Theodore Alexandrov
(T)
Ernest Arenas
(E)
Claudia Bagni
(C)
Robert Balderas
(R)
Andrea Bandelli
(A)
Burkhard Becher
(B)
Matthias Becker
(M)
Niko Beerenwinkel
(N)
Monsef Benkirame
(M)
Marc Beyer
(M)
Wendy Bickmore
(W)
Erik E A L Biessen
(EEAL)
Niklas Blomberg
(N)
Ingmar Blumcke
(I)
Bernd Bodenmiller
(B)
Barbara Borroni
(B)
Dimitrios T Boumpas
(DT)
Thomas Bourgeron
(T)
Sarion Bowers
(S)
Dries Braeken
(D)
Catherine Brooksbank
(C)
Nils Brose
(N)
Hilgo Bruining
(H)
Jo Bury
(J)
Nicolo Caporale
(N)
Giorgio Cattoretti
(G)
Nadia Chabane
(N)
Hervé Chneiweiss
(H)
Stuart A Cook
(SA)
Paolo Curatolo
(P)
Marien I de Jonge
(MI)
Bart Deplancke
(B)
Bart De Strooper
(B)
Peter de Witte
(P)
Stefanie Dimmeler
(S)
Bogdan Draganski
(B)
Anna Drews
(A)
Costica Dumbrava
(C)
Stefan Engelhardt
(S)
Thomas Gasser
(T)
Evangelos J Giamarellos-Bourboulis
(EJ)
Caroline Graff
(C)
Dominic Grün
(D)
Ivo Gut
(I)
Oskar Hansson
(O)
David C Henshall
(DC)
Anna Herland
(A)
Peter Heutink
(P)
Stephane R B Heymans
(SRB)
Holger Heyn
(H)
Meritxell Huch
(M)
Inge Huitinga
(I)
Paulina Jackowiak
(P)
Karin R Jongsma
(KR)
Laurent Journot
(L)
Jan Philipp Junker
(JP)
Shauna Katz
(S)
Jeanne Kehren
(J)
Stefan Kempa
(S)
Paulus Kirchhof
(P)
Christine Klein
(C)
Natalia Koralewska
(N)
Jan O Korbel
(JO)
Malte Kühnemund
(M)
Angus I Lamond
(AI)
Elsa Lauwers
(E)
Isabelle Le Ber
(I)
Ville Leinonen
(V)
Alejandro Lopez Tobon
(AL)
Emma Lundberg
(E)
Astrid Lunkes
(A)
Henrike Maatz
(H)
Matthias Mann
(M)
Luca Marelli
(L)
Vera Matser
(V)
Paul M Matthews
(PM)
Fatima Mechta-Grigoriou
(F)
Radhika Menon
(R)
Anne F Nielsen
(AF)
Massimiliano Pagani
(M)
R Jeroen Pasterkamp
(RJ)
Asla Pitkänen
(A)
Valentin Popescu
(V)
Cyril Pottier
(C)
Alain Puisieux
(A)
Rosa Rademakers
(R)
Dory Reiling
(D)
Orly Reiner
(O)
Daniel Remondini
(D)
Craig Ritchie
(C)
Jonathan D Rohrer
(JD)
Antoine-Emmanuel Saliba
(AE)
Raquel Sanchez-Valle
(R)
Amedeo Santosuosso
(A)
Arnold Sauter
(A)
Richard A Scheltema
(RA)
Philip Scheltens
(P)
Herbert B Schiller
(HB)
Anja Schneider
(A)
Philip Seibler
(P)
Kelly Sheehan-Rooney
(K)
David Shields
(D)
Kristel Sleegers
(K)
August B Smit
(AB)
Kenneth G C Smith
(KGC)
Ilse Smolders
(I)
Matthis Synofzik
(M)
Wai Long Tam
(WL)
Sarah Teichmann
(S)
Maria Thom
(M)
Margherita Y Turco
(MY)
Heleen M M van Beusekom
(HMM)
Rik Vandenberghe
(R)
Silvie Van den Hoecke
(S)
Ibo Van de Poel
(I)
Andre van der Ven
(A)
Julie van der Zee
(J)
Jan van Lunzen
(J)
Geert van Minnebruggen
(G)
Alexander van Oudenaarden
(A)
Wim Van Paesschen
(W)
John van Swieten
(J)
Remko van Vught
(R)
Matthijs Verhage
(M)
Patrik Verstreken
(P)
Carlo Emanuele Villa
(CE)
Jörg Vogel
(J)
Christof von Kalle
(C)
Jörn Walter
(J)
Sarah Weckhuysen
(S)
Wilko Weichert
(W)
Louisa Wood
(L)
Anette-Gabriele Ziegler
(AG)
Frauke Zipp
(F)
Commentaires et corrections
Type : ErratumIn
Références
Claussnitzer, M. et al. A brief history of human disease genetics. Nature 577, 179–189 (2020).
pubmed: 31915397
pmcid: 7405896
Karczewski, K. J. & Snyder, M. P. Integrative omics for health and disease. Nat. Rev. Genet. 19, 299–310 (2018).
pubmed: 29479082
pmcid: 5990367
Clevers, H. Modeling development and disease with organoids. Cell 165, 1586–1597 (2016).
pubmed: 27315476
Lancaster, M. A. & Knoblich, J. A. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345, 1247125 (2014).
pubmed: 25035496
Tanay, A. & Regev, A. Scaling single-cell genomics from phenomenology to mechanism. Nature 541, 331–338 (2017).
pubmed: 28102262
pmcid: 5438464
Regev, A. et al. The human cell atlas. eLife 6, e27041 (2017).
pubmed: 29206104
pmcid: 5762154
The LifeTime Initiative. LifeTime Strategic Research Agenda. https://lifetime-initiative.eu/wp-content/uploads/2020/08/LifeTime-Strategic-Research-Agenda.pdf (2020).
Yofe, I., Dahan, R. & Amit, I. Single-cell genomic approaches for developing the next generation of immunotherapies. Nat. Med. 26, 171–177 (2020).
pubmed: 32015555
HuBMAP Consortium. The human body at cellular resolution: the NIH Human Biomolecular Atlas Program. Nature 574, 187–192 (2019).
Guo, X. et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing. Nat. Med. 24, 978–985 (2018).
Ledergor, G. et al. Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma. Nat. Med. 24, 1867–1876 (2018).
pubmed: 30523328
Li, H. et al. Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176, 775–789.e718 (2019).
Puram, S. V. et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell 171, 1611–1624.e1624 (2017).
pubmed: 29198524
pmcid: 5878932
Tirosh, I. et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science 352, 189–196 (2016).
pubmed: 4944528
pmcid: 4944528
van Galen, P. et al. Single-cell RNA-seq reveals AML hierarchies relevant to disease progression and immunity. Cell 176, 1265–1281.e1224 (2019).
pubmed: 30827681
pmcid: 6515904
Der, E. et al. Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways. Nat. Immunol. 20, 915–927 (2019).
pubmed: 31110316
pmcid: 6584054
Zhang, F. et al. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry. Nat. Immunol. 20, 928–942 (2019).
pubmed: 31061532
pmcid: 31061532
Grubman, A. et al. A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation. Nat. Neurosci. 22, 2087–2097 (2019).
pubmed: 31768052
Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e1217 (2017).
pubmed: 28602351
Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 332–337 (2019).
pubmed: 6865822
pmcid: 6865822
Wang, L. et al. Single-cell reconstruction of the adult human heart during heart failure and recovery reveals the cellular landscape underlying cardiac function. Nat. Cell Biol. 22, 108–119 (2020).
pubmed: 31915373
Reyes, M. et al. An immune-cell signature of bacterial sepsis. Nat. Med. 26, 333–340 (2020).
pubmed: 32066974
pmcid: 7235950
Argelaguet, R. et al. Multi-omics profiling of mouse gastrulation at single-cell resolution. Nature 576, 487–491 (2019).
pubmed: 31827285
pmcid: 6924995
Clark, S. J. et al. scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells. Nat. Commun. 9, 781 (2018).
pubmed: 29472610
pmcid: 5823944
Rooijers, K. et al. Simultaneous quantification of protein–DNA contacts and transcriptomes in single cells. Nat. Biotechnol. 37, 766–772 (2019).
pubmed: 31209373
pmcid: 6609448
Chen, W. T. et al. Spatial transcriptomics and in situ sequencing to study Alzheimer’s disease. Cell 182, 976–991.e19 (2020).
pubmed: 32702314
Giladi, A. et al. Dissecting cellular crosstalk by sequencing physically interacting cells. Nat. Biotechnol. 38, 629–637 (2020).
Moffitt, J. R. et al. Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science 362, eaau5324 (2018).
pubmed: 30385464
pmcid: 6482113
Nitzan, M., Karaiskos, N., Friedman, N. & Rajewsky, N. Gene expression cartography. Nature 576, 132–137 (2019).
pubmed: 31748748
Ståhl, P. L. et al. Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 78–82 (2016).
pubmed: 27365449
van den Brink, S. C. et al. Single-cell and spatial transcriptomics reveal somitogenesis in gastruloids. Nature 582, 405–409 (2020).
pubmed: 32076263
Vickovic, S. et al. High-definition spatial transcriptomics for in situ tissue profiling. Nat. Methods 16, 987–990 (2019).
pubmed: 31501547
pmcid: 6765407
Bintu, B. et al. Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells. Science 362, eaau1783 (2018).
pubmed: 30361340
pmcid: 6535145
Cardozo Gizzi, A. M. et al. Microscopy-based chromosome conformation capture enables simultaneous visualization of genome organization and transcription in intact organisms. Mol. Cell. 74, 212–222.e215 (2019).
pubmed: 30795893
Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015).
pubmed: 25858977
pmcid: 4662681
Mateo, L. J. et al. Visualizing DNA folding and RNA in embryos at single-cell resolution. Nature 568, 49–54 (2019).
pubmed: 30886393
pmcid: 6556380
Medaglia, C. et al. Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq. Science 358, 1622–1626 (2017).
pubmed: 29217582
pmcid: 7234837
Jackson, H. W. et al. The single-cell pathology landscape of breast cancer. Nature 578, 615–620 (2020).
pubmed: 31959985
Keren, L. et al. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174, 1373–1387.e1319 (2018).
pubmed: 30193111
pmcid: 6132072
Maniatis, S. et al. Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis. Science 364, 89–93 (2019).
pubmed: 30948552
Baron, C. S. & van Oudenaarden, A. Unravelling cellular relationships during development and regeneration using genetic lineage tracing. Nat. Rev. Mol. Cell Biol. 20, 753–765 (2019).
pubmed: 31690888
Helmink, B. A. et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature 577, 549–555 (2020).
pubmed: 31942075
Krieg, C. et al. High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy. Nat. Med. 24, 144–153 (2018).
pubmed: 29309059
Kim, C. et al. Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing. Cell 173, 879–893.e813 (2018).
pubmed: 29681456
pmcid: 6132060
Rambow, F. et al. Toward minimal residual disease-directed therapy in melanoma. Cell 174, 843–855.e819 (2018).
pubmed: 30017245
Corcoran, R. B. & Chabner, B. A. Application of cell-free DNA analysis to cancer treatment. N. Engl. J. Med. 379, 1754–1765 (2018).
pubmed: 30380390
Eraslan, G., Avsec, Ž., Gagneur, J. & Theis, F. J. Deep learning: new computational modelling techniques for genomics. Nat. Rev. Genet. 20, 389–403 (2019).
pubmed: 30971806
Lähnemann, D. et al. Eleven grand challenges in single-cell data science. Genome Biol. 21, 31 (2020).
pubmed: 32033589
pmcid: 7007675
Topol, E. J. High-performance medicine: the convergence of human and artificial intelligence. Nat. Med. 25, 44–56 (2019).
pubmed: 30617339
Argelaguet, R. et al. Multi-Omics Factor Analysis—a framework for unsupervised integration of multi-omics data sets. Mol. Syst. Biol. 14, e8124 (2018).
pubmed: 29925568
pmcid: 6010767
Efremova, M. & Teichmann, S. A. Computational methods for single-cell omics across modalities. Nat. Methods 17, 14–17 (2020).
pubmed: 31907463
Pearl, J. & Mackenzie, D. The Book of Why: The New Science of Cause and Effect (Penguin, 2019).
Amin, N. D. & Paşca, S. P. Building models of brain disorders with three-dimensional organoids. Neuron 100, 389–405 (2018).
pubmed: 30359604
Knoblich, J. A. Lab-built brains. Sci. Am. 316, 26–31 (2016).
pubmed: 28004710
Bleijs, M., van de Wetering, M., Clevers, H. & Drost, J. Xenograft and organoid model systems in cancer research. EMBO J. 38, e101654 (2019).
pubmed: 31282586
pmcid: 6670015
Byrne, A. T. et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat. Rev. Cancer 17, 254–268 (2017).
pubmed: 28104906
Espuny-Camacho, I. et al. Hallmarks of Alzheimer’s disease in stem-cell-derived human neurons transplanted into mouse brain. Neuron 93, 1066–1081.e1068 (2017).
pubmed: 28238547
Hasselmann, J. et al. Development of a chimeric model to study and manipulate human microglia in vivo. Neuron 103, 1016–1033.e1010 (2019).
pubmed: 31375314
pmcid: 7138101
Mancuso, R. et al. Stem-cell-derived human microglia transplanted in mouse brain to study human disease. Nat. Neurosci. 22, 2111–2116 (2019).
pubmed: 31659342
Wilkinson, M. D. et al. The FAIR guiding principles for scientific data management and stewardship. Sci. Data 3, 160018 (2016).
pubmed: 26978244
pmcid: 4792175
Schultze, J. L.The SYSCID Consortium & Rosenstiel, P. Systems medicine in chronic inflammatory diseases. Immunity 48, 608–613 (2018).
pubmed: 29669240
Life Science RI European Life Science Research Infrastructures https://lifescience-ri.eu/home.html (2020).
Sugarman, J. & Bredenoord, A. L. Real-time ethics engagement in biomedical research: ethics from bench to bedside. EMBO Rep. 21, e49919 (2020).
pubmed: 31944538
pmcid: 7001493
Torres-Padilla, M. E. et al. Thinking ‘ethical’ when designing a new biomedical research consortium. EMBO J. 39, e105725 (2020).
pubmed: 32894572
pmcid: 7527923
European Commission. People in the EU: who are we and how do we live? https://ec.europa.eu/eurostat/documents/3217494/7089681/KS-04-15-567-EN-N.pdf/8b2459fe-0e4e-4bb7-bca7-7522999c3bfd (Eurostat, 2015).
What happened to personalized medicine? Nat. Biotechnol. 30, 1 (2012).