Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

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Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3. / Schmidt, Angelika; Marabita, Francesco; Kiani, Narsis A.; Gross, Catharina C.; Johansson, Henrik J.; Éliás, Szabolcs; Rautio, Sini; Eriksson, Matilda; Fernandes, Sunjay Jude; Silberberg, Gilad; Ullah, Ubaid; Bhatia, Urvashi; Lähdesmäki, Harri; Lehtiö, Janne; Gomez-Cabrero, David; Wiendl, Heinz; Lahesmaa, Riitta; Tegnér, Jesper.

In: BMC Biology, Vol. 16, No. 1, 47, 07.05.2018, p. 1-35.

Research output: Contribution to journalArticle

Harvard

Schmidt, A, Marabita, F, Kiani, NA, Gross, CC, Johansson, HJ, Éliás, S, Rautio, S, Eriksson, M, Fernandes, SJ, Silberberg, G, Ullah, U, Bhatia, U, Lähdesmäki, H, Lehtiö, J, Gomez-Cabrero, D, Wiendl, H, Lahesmaa, R & Tegnér, J 2018, 'Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3', BMC Biology, vol. 16, no. 1, 47, pp. 1-35. https://doi.org/10.1186/s12915-018-0518-3

APA

Schmidt, A., Marabita, F., Kiani, N. A., Gross, C. C., Johansson, H. J., Éliás, S., ... Tegnér, J. (2018). Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3. BMC Biology, 16(1), 1-35. [47]. https://doi.org/10.1186/s12915-018-0518-3

Vancouver

Author

Schmidt, Angelika ; Marabita, Francesco ; Kiani, Narsis A. ; Gross, Catharina C. ; Johansson, Henrik J. ; Éliás, Szabolcs ; Rautio, Sini ; Eriksson, Matilda ; Fernandes, Sunjay Jude ; Silberberg, Gilad ; Ullah, Ubaid ; Bhatia, Urvashi ; Lähdesmäki, Harri ; Lehtiö, Janne ; Gomez-Cabrero, David ; Wiendl, Heinz ; Lahesmaa, Riitta ; Tegnér, Jesper. / Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3. In: BMC Biology. 2018 ; Vol. 16, No. 1. pp. 1-35.

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@article{aa1dc7cbb06b4bea9c7c315d1a49bc7f,
title = "Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3",
abstract = "Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset. Conclusion: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.",
keywords = "Data integration, FOXP3, ITreg, Proteomics, Regulatory T cells, RNA sequencing (RNA-Seq), T cell differentiation, TGF-β, Treg",
author = "Angelika Schmidt and Francesco Marabita and Kiani, {Narsis A.} and Gross, {Catharina C.} and Johansson, {Henrik J.} and Szabolcs {\'E}li{\'a}s and Sini Rautio and Matilda Eriksson and Fernandes, {Sunjay Jude} and Gilad Silberberg and Ubaid Ullah and Urvashi Bhatia and Harri L{\"a}hdesm{\"a}ki and Janne Lehti{\"o} and David Gomez-Cabrero and Heinz Wiendl and Riitta Lahesmaa and Jesper Tegn{\'e}r",
year = "2018",
month = "5",
day = "7",
doi = "10.1186/s12915-018-0518-3",
language = "English",
volume = "16",
pages = "1--35",
journal = "BMC Biology",
issn = "1741-7007",
publisher = "BioMed Central",
number = "1",

}

RIS - Download

TY - JOUR

T1 - Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3

AU - Schmidt, Angelika

AU - Marabita, Francesco

AU - Kiani, Narsis A.

AU - Gross, Catharina C.

AU - Johansson, Henrik J.

AU - Éliás, Szabolcs

AU - Rautio, Sini

AU - Eriksson, Matilda

AU - Fernandes, Sunjay Jude

AU - Silberberg, Gilad

AU - Ullah, Ubaid

AU - Bhatia, Urvashi

AU - Lähdesmäki, Harri

AU - Lehtiö, Janne

AU - Gomez-Cabrero, David

AU - Wiendl, Heinz

AU - Lahesmaa, Riitta

AU - Tegnér, Jesper

PY - 2018/5/7

Y1 - 2018/5/7

N2 - Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset. Conclusion: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

AB - Background: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood. Results: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset. Conclusion: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.

KW - Data integration

KW - FOXP3

KW - ITreg

KW - Proteomics

KW - Regulatory T cells

KW - RNA sequencing (RNA-Seq)

KW - T cell differentiation

KW - TGF-β

KW - Treg

UR - http://www.scopus.com/inward/record.url?scp=85046436951&partnerID=8YFLogxK

U2 - 10.1186/s12915-018-0518-3

DO - 10.1186/s12915-018-0518-3

M3 - Article

VL - 16

SP - 1

EP - 35

JO - BMC Biology

JF - BMC Biology

SN - 1741-7007

IS - 1

M1 - 47

ER -

ID: 21094294