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> Haim Vilmovsky Liora >
Single-cell analysi...
Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation
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Proserpio, Valentina (author)
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Piccolo, Andrea (author)
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Haim-Vilmovsky, Liora (author)
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Kar, Gozde (author)
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Lönnberg, Tapio (author)
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Svensson, Valentine (author)
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Pramanik, Jhuma (author)
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Natarajan, Kedar Nath (author)
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Zhai, Weichao (author)
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Zhang, Xiuwei (author)
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Donati, Giacomo (author)
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Kayikci, Melis (author)
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Kotar, Jurij (author)
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McKenzie, Andrew N. J. (author)
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Montandon, Ruddy (author)
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- Billker, Oliver (author)
- Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK
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Woodhouse, Steven (author)
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Cicuta, Pietro (author)
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Nicodemi, Mario (author)
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Teichmann, Sarah A. (author)
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(creator_code:org_t)
- 2016-05-12
- 2016
- English.
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In: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X. ; 17
- Related links:
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https://umu.diva-por... (primary) (Raw object)
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https://genomebiolog...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- BACKGROUND: Differentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells.RESULTS: We perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing.CONCLUSION: The link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- CD4+ T cells
- Adaptive immunity
- Single-cell RNA-seq
- Cell cycle
- Differentiation
- Live imaging
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Proserpio, Valen ...
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Piccolo, Andrea
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Haim-Vilmovsky, ...
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Kar, Gozde
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Lönnberg, Tapio
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Svensson, Valent ...
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show more...
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Pramanik, Jhuma
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Natarajan, Kedar ...
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Zhai, Weichao
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Zhang, Xiuwei
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Donati, Giacomo
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Kayikci, Melis
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Kotar, Jurij
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McKenzie, Andrew ...
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Montandon, Ruddy
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Billker, Oliver
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Woodhouse, Steve ...
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Cicuta, Pietro
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Nicodemi, Mario
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Teichmann, Sarah ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Genome Biology
- By the university
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Umeå University