ArticleJournal of the Royal Society, Interface2013
Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence.
Article in Journal of the Royal Society, Interface, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Gene-regulatory programs that specify age-related differences during thymocyte development.Cell reports · 2025Article
- T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025Review
- Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024Review
- T-cell commitment inheritance-an agent-based multi-scale model.NPJ systems biology and applications · 2024Article
- Transcriptome-based measurement of CD8Trends in immunology · 2023Review
- Speed and navigation control of thymocyte development by the fetal T-cell gene regulatory network.Immunological reviews · 2023Review
- Multi-modular structure of the gene regulatory network for specification and commitment of murine T cells.Frontiers in immunology · 2023Review
- Logic and lineage impacts on functional transcription factor deployment for T-cell fate commitment.Biophysical journal · 2021Review
- Modeling the Dynamics of T-Cell Development in the Thymus.Entropy (Basel, Switzerland) · 2021Review
- Tunable, division-independent control of gene activation timing by a polycomb switch.Cell reports · 2021Article
- Single-cell insights into the hematopoietic generation of T-lymphocyte precursors in mouse and human.Experimental hematology · 2021Review
- How transcription factors drive choice of the T cell fate.Nature reviews. Immunology · 2021Review
- Multi-scale Dynamical Modeling of T Cell Development from an Early Thymic Progenitor State to Lineage Commitment.Cell reports · 2021Article
- An enriched network motif family regulates multistep cell fate transitions with restricted reversibility.PLoS computational biology · 2019Article
- Quantitative analysis reveals reciprocal regulations underlying recovery dynamics of thymocytes and thymic environment in mice.Communications biology · 2019Article
- Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development.Frontiers in immunology · 2019Review
- Exploring intermediate cell states through the lens of single cells.Current opinion in systems biology · 2018Article
- Cytokines, Transcription Factors, and the Initiation of T-Cell Development.Cold Spring Harbor perspectives in biology · 2018Review
- Fitting structure to function in gene regulatory networks.History and philosophy of the life sciences · 2017Article
- Asynchronous combinatorial action of four regulatory factors activates Bcl11b for T cell commitment.Nature immunology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Bone-marrow-derived progenitors must continually enter the thymus of an adult mouse to sustain T-cell homeostasis, yet only a few input cells per day are sufficient to support a yield of 5 × 10(7) immature T-cells per day and an eventual output of 1-2 × 10(6) mature cells per day. While substantial progress has been made to delineate the developmental pathway of T-cell lineage commitment, still little is known about the relationship between differentiation competence and the remarkable expansion of the earliest (DN1 stage) T-cell progenitors. To address this question, we developed computational models where the probability to progress to the next stage (DN2) is related to division number. To satisfy differentiation kinetics and overall cell yield data, our models require that adult DN1 cells divide multiple times before becoming competent to progress into DN2 stage. Our findings were subsequently tested by in vitro experiments, where putative early and later-stage DN1 progenitors from the thymus were purified and their progression into DN2 was measured. These experiments showed that the two DN1 sub-populations divided with similar rates, but progressed to the DN2 stage with different rates, thus providing experimental evidence that DN1 cells increase their commitment probability in a cell-intrinsic manner as they undergo cell division. Proliferation-linked shifts in eligibility of DN1 cells to undergo specification thus control kinetics of T-cell generation.
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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.