PXD015315

PXD015315 is an original dataset announced via ProteomeXchange.

Title	Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines
Description	Naïve CD4+ T cells coordinate the immune response by acquiring an effector phenotype in response to cytokines. However, the cytokine responses in memory T cells remain largely understudied. We used quantitative proteomics, bulk RNA-seq and single-cell RNA-seq of over 40,000 human naïve and memory CD4+ T cells to generate a detailed map of cytokine-regulated gene expression programs. We demonstrated that cytokine response differs substantially between naïve and memory T cells and showed that memory cells are unable to differentiate into the Th2 phenotype. Moreover, memory T cells acquire a Th17-like phenotype in response to iTreg polarization. At the single-cell level, we demonstrated that T cells form a continuum which progresses from naïve to effector memory T cells. This continuum is accompanied by a gradual increase in the expression levels of chemokines and cytokines and thus represents an effectorness gradient. Finally, we found that T cell cytokine responses are determined by where the cells lie in the effectorness gradient and identified genes whose expression is controlled by cytokines in an effectorness-dependent manner. Our results shed light on the heterogeneity of T cells and their responses to cytokines, provide insight into immune disease inflammation and could inform drug development.
HostingRepository	PRIDE
AnnounceDate	2020-03-04
AnnouncementXML	Submission_2020-05-27_05:14:38.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	James Wright
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-04 06:11:26	ID requested
1	2020-03-04 00:28:44	announced
⏵ 2	2020-05-27 05:14:39	announced	2020-05-27: Updated publication reference for PubMed record(s): 32286271.

Cano-Gamez E, Soskic B, Roumeliotis TI, So E, Smyth DJ, Baldrighi M, Will, é D, Nakic N, Esparza-Gordillo J, Larminie CGC, Bronson PG, Tough DF, Rowan WC, Choudhary JS, Trynka G, T cells to cytokines. Nat Commun, 11(1):1801(2020) [pubmed]

submitter keyword: Human, MS/MS, TMT

Jyoti Choudhary
contact affiliation	Institute of Cancer Research, London & Wellcome Trust Sanger Institute, Cambridge
contact email	jyoti.choudhary@icr.ac.uk
lab head
James Wright
contact affiliation	Functional Proteomics, Institute Cancer Research & Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute
contact email	jw13@sanger.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/03/PXD015315

PRIDE project URI

• PRIDE
  1. PXD015315
     1. Label: PRIDE project
     2. Name: Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines