ArticleGenome biology2016
Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
41 citing papers in PubMed, 69 citations in OpenAlex.
- Key Concepts in Transcriptomics Data Analysis in the Era of Next-Gen Sequencing.Advances in experimental medicine and biology · 2026Review
- Distribution modeling quantifies collective TScience advances · 2023Article
- Exploring the dynamics and influencing factors of CD4 T cell activation using single-cell RNA-seq.iScience · 2023Article
- Metabolism in type 2 immune responses.Immunity · 2023Review
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Th2 single-cell heterogeneity and clonal distribution at distant sites in helminth-infected mice.eLife · 2022Article
- T-Cell Receptor Repertoire Sequencing and Its Applications: Focus on Infectious Diseases and Cancer.International journal of molecular sciences · 2022Review
- A narrative review of research progress on the role ofAnnals of translational medicine · 2022Review
- Redefining intestinal immunity with single-cell transcriptomics.Mucosal immunology · 2022Review
- SkewC: Identifying cells with skewed gene body coverage in single-cell RNA sequencing data.iScience · 2022Article
- Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.Frontiers in immunology · 2022Article
- In chronic infection, HIV gag-specific CD4+ T cell receptor diversity is higher than CD8+ T cell receptor diversity and is associated with less HIV quasispecies diversity.Journal of virology · 2021Article
- Ribosome-Targeting Antibiotics Impair T Cell Effector Function and Ameliorate Autoimmunity by Blocking Mitochondrial Protein Synthesis.Immunity · 2021Article
- Article
- Predicting single-cell gene expression profiles of imaging flow cytometry data with machine learning.Nucleic acids research · 2020Article
- Mapping Cellular Coordinates through Advances in Spatial Transcriptomics Technology.Molecules and cells · 2020Review
- scds: computational annotation of doublets in single-cell RNA sequencing data.Bioinformatics (Oxford, England) · 2020Article
- Receptor signaling, transcriptional, and metabolic regulation of T cell exhaustion.Oncoimmunology · 2020Review
- Single Cell RNA-Sequencing for the Study of Atherosclerosis.Journal of lipid and atherosclerosis · 2019Review
- Single cell analysis of human foetal liver captures the transcriptional profile of hepatobiliary hybrid progenitors.Nature communications · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundDifferentiation 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.
resultsWe 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.
conclusionThe 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.