Structure of the endoplasmic reticulum during cell differentiation and stress

Abstract text (incl. figure legends and references)

The endoplasmic reticulum (ER) consists of an elaborate network of flat cisternae (aka sheets) and tubules that extends throughout the cell and occupies a large fraction of the cytoplasmic volume. The ER contributes to the production and folding of approximately one third of cellular proteins, has a key role in coordinating lipid biosynthesis, and constitutes a reservoir of Ca2+ ions that act as signalling molecules to regulate essential cellular processes. The ER has a central role in organelle communication as it forms membrane contacts with most other organelles. Specific ER stress signaling pathways, collectively known as the unfolded protein response (UPR), are required for maintaining ER homeostasis. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand. The UPR initially aims to restore ER homeostasis and normal cellular functions. However, prolonged UPR induces apoptosis to eliminate the defected cell. The continuity of the ER network, the extensive contacts with other organelles and its highly dynamic nature provides a mechanism to propagate various signals throughout the cell. The ER functions as a sensor of cell's well-being by integrating inter- and intracellular signals and inducing appropriate responses under various conditions during growth, division and differentiation.

The dynamic and complex organization of ER poses a major challenge on understanding how its functioning – maintenance of the structure, distribution of its functions and communication with other organelles – is orchestrated. We are utilizing CLEM and various volumeEM techniques in imaging of organelles, cells and tissue to carry out a detailed quantitative morphological characterization of the ER under physiological or pathological conditions such as ER stress, and during differentiation processes where cells adopt specialized functions. This will increase our understanding of fundamental aspects on the regulation of ER functioning and organization of the organelle communication.

Figure 1: hiPSC prior (left) and after (middle and right from stage 7) differentiation to pancreatic secretory cells. ER is depicted in yellow.