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Collective cell dynamics and morphogenesis in organoids

Collective cell dynamics and morphogenesis play a crucial role in many developmental and physiological contexts. In this work (bioRxiv 2022), we use murine pancreas-derived organoids to study tissue rotation, a multicellular phenomenon widely reported both in vivo and in vitro. Combining light sheet microscopy and custom-built computational framework, we quantify spatiotemporal tissue flows in 3D. Using a 3D vertex model, we demonstrate how the interplay between traction force and polarity alignment can account for distinct rotational dynamics observed in experiments. Our results show that the spherical tissue rotates as an active solid and exhibits spontaneous chiral symmetry breaking. Using a continuum model, we demonstrate how the types and location of topological defects in the polarity field underlie this symmetry breaking process. Altogether, our work shows that tissue chirality can arise via topological defects in the pattern of cell traction forces, with potential implications for left-right symmetry breaking processes in morphogenetic events.

Aside from collective cell dynamics in organoids, an active area of research in the lab is the problem of morphogenesis. Specifically, we are interested in to chart the ‘morphological landscape’ using a big data approach, and from it, extract tissue self-assembly rules used in shape programming during animal development. This is analogous to how transcriptomic landscape can be used to identify cell types and extract gene regulatory circuits. To achieve this, we will make use of organoid (an accessible multicellular system that mimics development and generates a wide variety of shape features) and develop novel computational tools. Once we have access to these tissue self-assembly rule, we will be able to manipulate organoid morphogenesis using synthetic biology tools such as optogenetics. These ideas are discussed further in the perspective article (Sem. in Cell. Dev. Bio. 2022).


Rotating single-epithelial pancreas organoid.


Morphological landscape (analagous to transcriptomic landscape) reveals the principal shape modes of organoid.

Related publication:

  1. Tan TH*, Amiri A*, Barandiaran IS*, Staddon M, Hermann A, Tomas S, Duclut C, Papovic M, Julicher F, Grapin-Botton A. “Emergent chirality in active solid rotation of pancreas spheres.” bioRxiv 2022.

  2. Tan TH*, Liu J*, Grapin-Botton A. "Mapping and exploring the organoid state space using synthetic biology." Seminars in Cell and Developmental Biology (2022). Academic Press.

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