Stem cells exhibit exceptionally prominent transcriptional clusters, which dissolve with progressing differentiation. Although these clusters are assigned central roles in embryonic gene regulation, their formation and loss during differentiation remain poorly understood. This study reveals that these prominent clusters disperse along a conserved trajectory in mouse embryonic stem cells, fruit fly testes, and zebrafish embryos. Imaging and lattice simulations show that these clusters form via surface condensation on H3K27ac-marked super-enhancer regions, which act as genomic scaffolds. Upon differentiation, partial loss of these active epigenetic marks and transcription-driven unfolding lead to dispersal of the prominent clusters. The block copolymer-based lattice simulations explain this process as a conserved trajectory through a three-dimensional state space, governed by surface condensation principles that extend beyond canonical liquid–liquid phase separation. This work marks surface condensation as a biophysical mechanism for the dynamic organization of stem cell-specific transcriptional hubs and demonstrates evolutionary conservation in several organisms. By uncovering a conserved biophysical mechanism for transcriptional organization in development, our work illustrates how polymer properties can contribute to the control of cell identity and fate.
Cellular aggregate formation: Continuum modelling and computational aspects
Soheil Firooz,
B. Daya Reddy,
Vasily Zaburdaev,
Paul Steinmann
Computer Methods in Applied Mechanics and Engineering
451
118687
(2026)
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In this manuscript, we carry out a systematic study on the mechanics and rheology of cellular aggregate formations. We study how cell–cell and cell–matrix interactions influence cellular aggregation, which can be described as an active phase separation process. Furthermore, we investigate the mechanisms underlying the coalescence of aggregates. The problem is analyzed in both Eulerian and Lagrangian frameworks and the computational intricacies for each approach are highlighted. Using our recently developed micromorphic-based artificial diffusion method, we circumvent the numerical instabilities arising from the convective nature of the problem. Finally, via a comprehensive numerical study, we investigate the dynamics of the cellular aggregate formation under various conditions. A notable agreement between the numerical and experimental results is observed. Our work provides significant insights into the mechanics of cellular aggregates which paves the way for better understanding the role of active mechanical forces in biological systems.
Kontakt
Abteilung Immunophysik Prof. Vasily Zaburdaev Principal Investigator
Max-Planck-Zentrum für Physik und Medizin Kussmaulallee 2 Raum 02.116 91054 Erlangen 09131 8284 102
