Modeling cell-specific dynamics and regulation of the common gamma chain cytokines

Farhat, Ali M.; Weiner, Adam C.; Posner, Cori; Kim, Zoe S; Orcutt-Jahns, Brian T; Carlson, Scott M.; Meyer, Aaron S.

doi:10.1016/j.celrep.2021.109044

Cited by 16 publications

(45 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, our experimental studies highlighted the large variability in the abundance of signaling components (receptors, kinases, phosphatases, etc. ), even within isogenic population of cells (4, 5). In fact, this variability drives some phenotypic heterogeneity (4, 5, 15, 16).…”

Section: Resultsmentioning

confidence: 99%

“…), even within isogenic population of cells (4, 5). In fact, this variability drives some phenotypic heterogeneity (4, 5, 15, 16). We simulated cellular populations for each of the arrangements, with the distribution of each protein described by a lognormal distribution with a CV of 0.25 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…(receptors, kinases, phosphatases, etc. ), even within isogenic population of cells (4,5). In fact, this variability drives some phenotypic heterogeneity (4,5,15,16).…”

Section: R a F Tmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted October 7, 2022. ; https://doi.org/10.1101/2022.10.07.511173 doi: bioRxiv preprint D R A F T population of cells (4,5). We, thus, combined single-cell experimental measurements and mathematical modeling to explore the impact of the relative abundance of signaling components on the sensitivity and amplitude in response to extra-cellular cytokines (6,7).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Tuning of cytokine signaling through imbalanced abundances of receptors and kinases

Sta

Voisinne

Cotari³

et al. 2022

Preprint

View full text Add to dashboard Cite

Cells rely on cytokines to coordinate their activation, differentiation, proliferation and survival. In particular, γC cytokines (interleukins IL-2, 4, 7, 9, 15, and 21) regulate the fate of leukocytes. The signaling cascade induced by these cytokines is relatively simple, and involves the phosphorylation of receptor-associated Janus-like kinases (JAK). Here, we explore the cell-to-cell variability of cytokine responses in primary mouse T~cells, and find a paradoxical and quantitative imprint of receptor expression levels and other signaling components. For instance, high abundance of the common $\gamma_c$ chain reduces cytokine responses (both in terms of signaling amplitudes and characteristic cytokine concentrations triggering 50% of the response). We develop mathematical models to quantify how limited abundances of signaling components (e.g. JAK or other cytokine receptor subunit chains) may explain our experimental observations. We conclude by generalizing this observation of cell-to-cell signaling variability to other ligand-receptor-kinase systems.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…(receptors, kinases, phosphatases, etc. ), even within isogenic population of cells (4,5). In fact, this variability drives some phenotypic heterogeneity (4,5,15,16).…”

Section: R a F Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tuning of cytokine signaling through imbalanced abundances of receptors and kinases

Sta

Voisinne

Cotari³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Indeed, here, we have arranged data both with subject, antigen, and receptor modes, in either a coupled form (Fig 1 ) or a single tensor (Fig 6A ). With longitudinal data in which time points can be aligned, one could create a mode representing the contribution of time (Chitforoushzadeh et al , 2016 ; Farhat et al , 2021 ). Although each antigen is treated similarly along one dimension, antigenic mutants or strains could also be separated into separate tensor modes before decomposition.…”

Section: Discussionmentioning

confidence: 99%

Tensor‐structured decomposition improves systems serology analysis

Tan

Murphy

Alpay

et al. 2021

Molecular Systems Biology

Self Cite

View full text Add to dashboard Cite

Systems serology provides a broad view of humoral immunity by profiling both the antigen‐binding and Fc properties of antibodies. These studies contain structured biophysical profiling across disease‐relevant antigen targets, alongside additional measurements made for single antigens or in an antigen‐generic manner. Identifying patterns in these measurements helps guide vaccine and therapeutic antibody development, improve our understanding of diseases, and discover conserved regulatory mechanisms. Here, we report that coupled matrix–tensor factorization (CMTF) can reduce these data into consistent patterns by recognizing the intrinsic structure of these data. We use measurements from two previous studies of HIV‐ and SARS‐CoV‐2‐infected subjects as examples. CMTF outperforms standard methods like principal components analysis in the extent of data reduction while maintaining equivalent prediction of immune functional responses and disease status. Under CMTF, model interpretation improves through effective data reduction, separation of the Fc and antigen‐binding effects, and recognition of consistent patterns across individual measurements. Data reduction also helps make prediction models more replicable. Therefore, we propose that CMTF is an effective general strategy for data exploration in systems serology.

show abstract

Modeling cell-specific dynamics and regulation of the common gamma chain cytokines

Cited by 16 publications

References 64 publications

Tuning of cytokine signaling through imbalanced abundances of receptors and kinases

Tuning of cytokine signaling through imbalanced abundances of receptors and kinases

Tensor‐structured decomposition improves systems serology analysis

Engineered human cytokine/antibody fusion proteins expand regulatory T cells and confer autoimmune disease protection

Contact Info

Product

Resources

About