Kinetic models of hematopoietic differentiation

Research output: Contribution to journalReview article

Abstract

As cell and molecular biology is becoming increasingly quantitative, there is an upsurge of interest in mechanistic modeling at different levels of resolution. Such models mostly concern kinetics and include gene and protein interactions as well as cell population dynamics. The final goal of these models is to provide experimental predictions, which is now taking on. However, even without matured predictions, kinetic models serve the purpose of compressing a plurality of experimental results into something that can empower the data interpretation, and importantly, suggesting new experiments by turning "knobs" in silico. Once formulated, kinetic models can be executed in terms of molecular rate equations for concentrations or by stochastic simulations when only a limited number of copies are involved. Developmental processes, in particular those of stem and progenitor cell commitments, are not only topical but also particularly suitable for kinetic modeling due to the finite number of key genes involved in cellular decisions. Stem and progenitor cell commitment processes have been subject to intense experimental studies over the last decade with some emphasis on embryonic and hematopoietic stem cells. Gene and protein interactions governing these processes can be modeled by binary Boolean rules or by continuous-valued models with interactions set by binding strengths. Conceptual insights along with tested predictions have emerged from such kinetic models. Here we review kinetic modeling efforts applied to stem cell developmental systems with focus on hematopoiesis. We highlight the future challenges including multi-scale models integrating cell dynamical and transcriptional models. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Developmental Biology > Stem Cell Biology and Regeneration.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell Biology

Keywords

  • energy landscapes, hematopoiesis, rate equations, reprogramming, stem cells, stochastic simulations, systems biology
Original languageEnglish
Pages (from-to)e1424
JournalWiley interdisciplinary reviews. Systems biology and medicine
Volume11
Issue number1
Publication statusPublished - 2019
Publication categoryResearch
Peer-reviewedYes