Mapping Differentiation under Mixed Culture Conditions Reveals a Tunable Continuum of T Cell Fates

An experimental and theoretical study of T cell differentiation in response to mixed-input conditions reveals that cells can tune between Th1 and Th2 states through a continuum of mixed phenotypes.

[1]  Thomas Höfer,et al.  Stable T-bet+GATA-3+ Th1/Th2 Hybrid Cells Arise In Vivo, Can Develop Directly from Naive Precursors, and Limit Immunopathologic Inflammation , 2013, PLoS biology.

[2]  Alexander van Oudenaarden,et al.  Stochastic Cytokine Expression Induces Mixed T Helper Cell States , 2013, PLoS biology.

[3]  Kate Smith-Miles,et al.  Mathematical modelling of stem cell differentiation: the PU.1–GATA-1 interaction , 2012, Journal of mathematical biology.

[4]  Sean C. Bendall,et al.  Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. , 2012, Immunity.

[5]  W. Paul,et al.  An updated view on transcription factor GATA3-mediated regulation of Th1 and Th2 cell differentiation. , 2011, International immunology.

[6]  John J. Tyson,et al.  A Mathematical Model for the Reciprocal Differentiation of T Helper 17 Cells and Induced Regulatory T Cells , 2011, PLoS Comput. Biol..

[7]  S. Teichmann,et al.  RNA sequencing reveals two major classes of gene expression levels in metazoan cells , 2011, Molecular systems biology.

[8]  Sean C. Bendall,et al.  Single-Cell Mass Cytometry of Differential Immune and Drug Responses Across a Human Hematopoietic Continuum , 2011, Science.

[9]  Gordon Keller,et al.  Stage-specific optimization of activin/nodal and BMP signaling promotes cardiac differentiation of mouse and human pluripotent stem cell lines. , 2011, Cell stem cell.

[10]  Sui Huang,et al.  Understanding gene circuits at cell-fate branch points for rational cell reprogramming. , 2011, Trends in genetics : TIG.

[11]  J. Audet.  Adventures in time and space: Nonlinearity and complexity of cytokine effects on stem cell fate decisions. , 2010, Biotechnology and bioengineering.

[12]  Sui Huang,et al.  Cell Lineage Determination in State Space: A Systems View Brings Flexibility to Dogmatic Canonical Rules , 2010, PLoS biology.

[13]  Andreas Radbruch,et al.  Short-term memory in gene induction reveals the regulatory principle behind stochastic IL-4 expression , 2010, Molecular systems biology.

[14]  W. Paul,et al.  Differentiation of effector CD4 T cell populations (*). , 2010, Annual review of immunology.

[15]  Dan R. Littman,et al.  Th17 and Regulatory T Cells in Mediating and Restraining Inflammation , 2010, Cell.

[16]  Andreas Radbruch,et al.  Interferons direct Th2 cell reprogramming to generate a stable GATA-3(+)T-bet(+) cell subset with combined Th2 and Th1 cell functions. , 2010, Immunity.

[17]  Timothy J. Ross,et al.  Fuzzy Logic with Engineering Applications: Ross/Fuzzy Logic with Engineering Applications , 2010 .

[18]  Pavol Bokes,et al.  A bistable genetic switch which does not require high co-operativity at the promoter: a two-timescale model for the PU.1-GATA-1 interaction. , 2009, Mathematical medicine and biology : a journal of the IMA.

[19]  Andreas Radbruch,et al.  Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. , 2009, Immunity.

[20]  C. Peterson,et al.  Stem cell states, fates, and the rules of attraction. , 2009, Cell stem cell.

[21]  Yuka Kanno,et al.  Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. , 2009, Immunity.

[22]  Carsten Peterson,et al.  Computational Modeling of the Hematopoietic Erythroid-Myeloid Switch Reveals Insights into Cooperativity, Priming, and Irreversibility , 2009, PLoS Comput. Biol..

[23]  T. Graf,et al.  Heterogeneity of embryonic and adult stem cells. , 2008, Cell stem cell.

[24]  Rob J. de Boer,et al.  From the two-dimensional Th1 and Th2 phenotypes to high-dimensional models for gene regulation. , 2008 .

[25]  Remy Chait,et al.  Drug interactions modulate the potential for evolution of resistance , 2008, Proceedings of the National Academy of Sciences.

[26]  V. Kuchroo,et al.  Induction and effector functions of TH17 cells , 2008, Nature.

[27]  Hannah H. Chang,et al.  Transcriptome-wide noise controls lineage choice in mammalian progenitor cells , 2008, Nature.

[28]  U. Alon,et al.  Diverse two-dimensional input functions control bacterial sugar genes. , 2008, Molecular cell.

[29]  Shu Chien,et al.  Combinatorial signaling microenvironments for studying stem cell fate. , 2008, Stem cells and development.

[30]  R. Callard,et al.  Decision‐making by the immune response , 2007, Immunology and cell biology.

[31]  Sui Huang,et al.  Bifurcation dynamics in lineage-commitment in bipotent progenitor cells. , 2007, Developmental biology.

[32]  D. Loebel,et al.  Gene function in mouse embryogenesis: get set for gastrulation , 2007, Nature Reviews Genetics.

[33]  P. Hodgkin.  A probabilistic view of immunology: Drawing parallels with physics , 2007, Immunology and cell biology.

[34]  Megan N. McClean,et al.  Cross-talk and decision making in MAP kinase pathways , 2007, Nature Genetics.

[35]  Nir Friedman,et al.  Linking stochastic dynamics to population distribution: an analytical framework of gene expression. , 2006, Physical review letters.

[36]  Yoav Soen,et al.  Exploring the regulation of human neural precursor cell differentiation using arrays of signaling microenvironments , 2006, Molecular systems biology.

[37]  Luis Mendoza,et al.  A network model for the control of the differentiation process in Th cells. , 2006, Bio Systems.

[38]  Ingo Roeder,et al.  Towards an understanding of lineage specification in hematopoietic stem cells: a mathematical model for the interaction of transcription factors GATA-1 and PU.1. , 2006, Journal of theoretical biology.

[39]  S. Bhatia,et al.  An extracellular matrix microarray for probing cellular differentiation , 2005, Nature Methods.

[40]  Jaroslav Stark,et al.  Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. , 2004, Journal of theoretical biology.

[41]  Andreas Radbruch,et al.  Transcriptional control networks of cell differentiation: insights from helper T lymphocytes. , 2004, Progress in biophysics and molecular biology.

[42]  Ertugrul M. Ozbudak,et al.  Multistability in the lactose utilization network of Escherichia coli , 2004, Nature.

[43]  W. Paul,et al.  Probabilistic regulation of IL-4 production in Th2 cells: accessibility at the Il4 locus. , 2004, Immunity.

[44]  A B Cantor,et al.  Hematopoietic development: a balancing act. , 2001, Current opinion in genetics & development.

[45]  Stuart H. Orkin,et al.  Diversification of haematopoietic stem cells to specific lineages , 2000, Nature Reviews Genetics.

[46]  D. Hume,et al.  Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. , 2000, Blood.

[47]  L. Yang.  Fuzzy Logic with Engineering Applications , 1999 .

[48]  D. Littman,et al.  Regulation of IL-4 expression by activation of individual alleles. , 1998, Immunity.

[49]  M. Croft,et al.  Generation, persistence, and modulation of Th0 effector cells: role of autocrine IL-4 and IFN-gamma. , 1998, Journal of immunology.

[50]  T. Enver,et al.  The lineage commitment of haemopoietic progenitor cells. , 1997, Current opinion in genetics & development.

[51]  A. Kelso.  Th1 and Th2 subsets: paradigms lost? , 1995, Immunology today.

[52]  D. Metcalfe,et al.  Flow cytometric analysis for cytokine production identifies T helper 1, T helper 2, and T helper 0 cells within the human CD4+CD27- lymphocyte subpopulation. , 1995, Journal of immunology.

[53]  A. Kelso,et al.  Evidence for the stochastic acquisition of cytokine profile by CD4+ T cells activated in a T helper type 2‐like response in vivo , 1995, European journal of immunology.

[54]  K. Murphy,et al.  Heterogeneity of single cell cytokine gene expression in clonal T cell populations , 1994, The Journal of experimental medicine.