Biology subjects

Suppinger, S.

Publications and source records attributed to Suppinger, S..

3 recordsLinked to original sources

bioRxiv2023

Dynamics and plasticity of stem cells in the regenerating human colonic epithelium

The human intestinal epithelium is a tissue with rapid turnover. Its complex regenerative process and differentiation trajectories have been challenging to study due to its inaccessibility and lack of temporal sampling. To this end, we developed a workflow to culture adult stem cell-derived human intestinal organoids from single cells to maturation. Extensive characterization of our model system indicated a transient regenerative response, followed by differentiation into all mature cell lineages. This switch is accompanied by a transition between two stem cell states. High-content screening and comparison to in vivo studies revealed that an initial fetal-like state is crucial for achieving successful regeneration, while the subsequent adult-like state is vital for maintaining a balance of cell lineages and continuous support of crypt-morphogenesis. Taken together, this study highlights the extensive plasticity of the intestinal epithelium and paves the way for further studies of human intestinal regeneration and its deregulation in pathologies.

cell biology↗

bioRxiv2023

Open top multi sample dual view light sheet microscope for live imaging of large multicellular systems

Multicellular systems grow over the course of weeks from single cells to tissues or even full organisms composed of several thousands of cells, making live imaging of such samples challenging. To bridge these wide spatiotemporal scales, we present an open top dual view and dual illumination light sheet microscope dedicated for live imaging of large specimens at single cell resolution. The novel configuration of objectives together with a flexible and customizable multi-well mounting system combines dual view with high throughput multi-position imaging. We use the newly developed microscope to image a wide variety of samples and highlight its capabilities to gain quantitative single-cell information in large specimens such as mature intestinal organoids and gastruloids.

developmental biology↗

bioRxiv2021

An intrinsic temporal order of c-Jun N-terminal phosphorylation regulates its activity by orchestrating co-factor recruitment

Protein phosphorylation is a major regulatory mechanism of cellular signalling. The c-Jun proto-oncoprotein is phosphorylated at four residues within its transactivation domain (TAD) by the JNK family kinases, but the functional significance of c-Jun multisite phosphorylation has remained elusive. Here we show that c-Jun phosphorylation by JNK exhibits a defined temporal kinetics, with serine63 and serine73 being phosphorylated more rapidly than threonine91 and threonine93. We identified the positioning of the phosphorylation sites relative to the kinase docking motif, and their primary sequence, as the main factors controlling phosphorylation kinetics. Functional analysis revealed three c-Jun phosphorylation states: unphosphorylated c-Jun recruits the Mbd3 repressor, serine63/73 doubly-phosphorylated c-Jun binds to the Tcf4 co-activator, whereas the fully phosphorylated form disfavours Tcf4 binding attenuating JNK signalling. Thus, c-Jun phosphorylation encodes multiple functional states that drive a complex signalling response from a single JNK input.

biochemistry↗