Cells in vivo organize into 3D structures that underlie the shape and mechanics of tissues, as well as their biological function. Researchers mapped how mesenchymal stromal cells organize into organoids, by building a multiscale description based on massive single-cell data from microfluidic experiments. They found that cells organize into a core-shell structure that couples their level of commitment, cell-cell junctions and biological functions.
In vivo, cells self-organize into 3D structures that determine the shape and mechanics of tissues. The 3D organization within tissues and organs also regulates the level of production of signaling molecules by the cells, depending on their position and the position of their neighbors. Along these lines organoids have emerged as useful models to study cellular organization in highly relevant 3D cultures. However, understanding the factors that determine the cell positions and how this position affects their biological function remains challenging.
Researchers mapped how human mesenchymal stromal cells (MSCs) self-organize within 3D organoids. This population of mesenchymal progenitors is composed of a heterogeneous mixture of cells with different sizes and variable levels of commitment. The experiments leverage recent microfluidic developments that allowed them to obtain single-cell imaging data that resolve cellular positions and protein expressions on hundreds of thousands of cells, while preserving the information on their location within thousands of organoids. They were thus able to build a multiscale model of the cells within their environment.
They found that the most undifferentiated MSCs cluster in the center of the 3D aggregate while partially committed cells form a shell around them. This core-shell structure is also observed in the quality of cell-cell junctions, namely through different actin-cadherin interactions between the core and the shell. This in turn translates to different biological function of the cells, with the outer layers accounting for most of the production of some key osteo-endocrine molecules (VEGF-A, PGE-2). We identify the regulation of NF-kB, which is determined by the quality of cell-cell junctions, as a mechanism that links the structure to the biological function.
These results show a strong link between physical structure and biological function that is expected to be present in many organoids and tissues.