TY - INPR A1 - Kunze-Schumacher, Heike A1 - Verheyden, Nikita A. A1 - Grewers, Zoe A1 - Meyer-Hermann, Michael A1 - Greiff, Victor A1 - Robert, Philippe A. A1 - Krueger, Andreas T1 - High-resolution mapping of cell-cycle dynamics during steady-state T-cell development and regeneration in vivo T2 - bioRxiv N2 - Control of cell proliferation is critical for the lymphocyte life cycle. However, little is known on how stage-specific alterations in cell-cycle behavior drive proliferation dynamics during T-cell development. Here, we employed in vivo dual-nucleoside pulse labeling combined with determination of DNA replication over time as well as fluorescent ubiquitination-based cell-cycle indicator mice to establish a quantitative high-resolution map of cell-cycle kinetics of thymocytes. We developed an agent-based mathematical model of T-cell developmental dynamics. To generate the capacity for proliferative bursts, cell-cycle acceleration followed a 'stretch model', characterized by simultaneous and proportional contraction of both G1 and S phase. Analysis of cell-cycle phase dynamics during regeneration showed tailored adjustments of cell-cycle phase dynamics. Taken together, our results highlight intrathymic cell-cycle regulation as an adjustable system to maintain physiologic tissue homeostasis and foster our understanding of dysregulation of the T-cell developmental program. Y1 - 2023 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74334 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-743341 IS - 2023.06.14.544919 ER -