Intestinal Stem Cell Biology in Homeostasis and Cancer

1 PhD project offered in the IPP summer call 2022

Scientific Background

The adult small intestine has many vital functions, including absorption of nutrients, secretion of hormones and barrier in host defence against microorganisms. These functions of the small intestine depend on the correct specification and maintenance of differentiated cell types within the columnar epithelium. Enterocytes, which process and absorb nutrients, comprise the major cell population of the intestinal epithelium. The next largest group is goblet cells that secret protective mucus. Paneth cells expressing anti-microbial peptides as well as growth factors are part of the stem cell niche. Tuft cells are part of type 2 immunity. Various enteroendocrine cells secreting more than 20 hormones make the small intestine the largest endocrine organ. The intestinal epithelium is exposed to a harsh environment: microorganisms, xenobiotics, and food metabolites. As a result, the epithelial cells need to be rapidly replaced. To maintain tissue homeostasis, intestinal stem cells (ISCs) support continuous renewal of the epithelium.

PhD project: Functions of endothelial cells during differentiation of intestinal stem cells

Intestinal stem cells and their progenies receive multiple signals from the surrounding non-epithelial cells, such as fibroblasts and immune cells. Yet, it remains unknown how endothelial cells regulate differentiation of the intestinal epithelium. The gut endothelium is a complex paracrine organ. The crosstalk between the gut epithelium and endothelium is essential for the remodelling of the gut microbiota to protect against diet‐induced obesity. Using genetically modified mouse models, organoids, single-cell RNA-sequencing, proteomics, flow cytometry and confocal microscopy you will define signals secreted by the gut endothelium that modulate the differentiation capacity of intestinal stem cells.

Publications relevant to the project

Bayer F, Dremova O, Khuu MP, Mammadova K, Pontarollo G, Kiouptsi K, Soshnikova N, May-Simera HL, Endres K, Reinhardt C. (2021) The Interplay between Nutrition, Innate Immunity, and the Commensal Microbiota in Adaptive Intestinal Morphogenesis.Nutrients. 13: 2198. doi: 10.3390/nu13072198.

Sayols S, Klassek J, Werner C, Möckel S, Ritz S, Mendez-Lago M and Soshnikova N. (2020). Signalling codes for the maintenance and lineage commitment of embryonic gastric epithelial progenitors. Development. DOI: 10.1242/dev.188839.

Dzama MM, Nigmatullina L, Sayols S, Kreim N and Soshnikova N. (2017). Distinct populations of embryonic epithelial progenitors generate Lgr5+ intestinal stem cells. Dev Biol. 432: 258-264.

Kazakevych J, Sayols S, Messner B, Krienke C and Soshnikova N. (2017). Dynamic changes in chromatin states during specification and differentiation of adult intestinal stem cells. Nucleic Acids Res. 45: 5770–5784.

Nigmatullina L, Norkin M, Dzama MM, Messner B, Sayols S and Soshnikova N. (2017). Id2 controls specification of Lgr5(+) intestinal stem cell progenitors during gut development. TheEMBO J. 36: 869–885.

Contact Details

Dr. Natalia Soshnikova

Institute for Molecular Medicine
University Medical Center Mainz