ArticleBiophysical journal2008
Positive receptor feedback during lineage commitment can generate ultrasensitivity to ligand and confer robustness to a bistable switch.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Data-driven modeling predicts gene regulatory network dynamics during the differentiation of multipotential hematopoietic progenitors.PLoS computational biology · 2022Article
- Ultrasensitivity and bistability in covalent-modification cycles with positive autoregulation.Proceedings. Mathematical, physical, and engineering sciences · 2021Article
- Dynamic Modeling of Transcriptional Gene Regulatory Networks.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Determinants of transcription factor regulatory range.Nature communications · 2020Article
- Classification-Based Inference of Dynamical Models of Gene Regulatory Networks.G3 (Bethesda, Md.) · 2019Article
- Variable cellular decision-making behavior in a constant synthetic network topology.BMC bioinformatics · 2019Article
- Towards a Quantitative Understanding of Cell Identity.Trends in cell biology · 2018Review
- Robust hematopoietic progenitor cell commitment in the presence of a conflicting cue.Journal of cell science · 2015Article
- The osteogenic effect of erythropoietin on human mesenchymal stromal cells is dose-dependent and involves non-hematopoietic receptors and multiple intracellular signaling pathways.Stem cell reviews and reports · 2014Article
- Ultrasensitive response motifs: basic amplifiers in molecular signalling networks.Open biology · 2013Review
- Asymmetry in erythroid-myeloid differentiation switch and the role of timing in a binary cell-fate decision.Frontiers in immunology · 2013Article
- Optimal homeostasis necessitates bistable control.Journal of the Royal Society, Interface · 2012Article
- Human erythropoietin gene delivery using an arginine-grafted bioreducible polymer system.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Non-transcriptional regulatory processes shape transcriptional network dynamics.Nature reviews. Microbiology · 2011Review
- Robust network topologies for generating switch-like cellular responses.PLoS computational biology · 2011Article
- Synthetic conversion of a graded receptor signal into a tunable, reversible switch.Molecular systems biology · 2011Article
- Bimodal gene expression in noncooperative regulatory systems.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated suppression of toll-like receptor stimulated B-lymphocyte activation and initiation of plasmacytic differentiation.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- A bistable switch underlying B-cell differentiation and its disruption by the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- Stochastic modeling of B lymphocyte terminal differentiation and its suppression by dioxin.BMC systems biology · 2010Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokines and lineage-specific transcription factors are critical molecular effectors for terminal differentiation during hematopoiesis. Intrinsic transcription factor activity is often believed to drive commitment and differentiation, whereas cytokine receptor signals have been implicated in the regulation of cell proliferation, survival, and differentiation. In erythropoiesis, recent experimental findings provide direct evidence that erythropoietin (Epo) can generate commitment cues via the erythropoietin receptor (EpoR); specifically, EpoR signaling leads to activation of the transcription factor GATA-1, which then triggers transcription of erythrocyte-specific genes. In particular, activated GATA-1 induces two positive feedback loops in the system through the enhanced expression of both inactive GATA-1 and EpoR, the latter of which is externally regulatable by Epo. Based upon this network architecture, we present a mathematical model of GATA-1 activation by EpoR, which bidirectionally links a lineage-specific receptor and transcription factor. Our deterministic model offers insight into stimulus-response relationships between Epo and several downstream effectors. In addition to the survival signals that EpoR provides, steady-state analysis of our model suggests that receptor upregulation during lineage commitment can also generate ultrasensitivity to Epo and bistability in GATA-1 activity. These system-level properties can induce a switch-like characteristic during differentiation and provide robustness to the mature state. The topology also suggests a novel mechanism for achieving robust bistability in a purely deterministic manner without molecular cooperativity. The analytical solution of a generalized, minimal model is provided and the significance of each of the two positive feedback loops is elucidated through bifurcation analysis. This network topology, or variations thereof, may link other receptor-transcription factor pairs and may therefore be of general relevance in cellular decision-making.
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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.