New discoveries on intestinal epithelium maintenance
Now, a paper has been published by Professor Kim Bak Jensen’s group at the Copenhagen node of the Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW, in the journal Developmental Cell that provides new discoveries into the way the epithelium works.
The research began five years ago when a talented PhD student, and the paper’s first author, Isidora Banjac, joined the Jensen group with a desire to use mouse models to understand how the intestinal epithelium is renewed on a daily basis.
“The baseline for all studies is to understand what is normal. Once we understand that, we can begin to decipher what happens in disease,” said Professor Kim Bak Jensen.
The study reveals how simple rules govern the maintenance of one of our most vital organs for nutrient absorption throughout life. Intestinal stem cells, found at the base of crypts in specialised environments called niches, face three distinct options. They can 1) divide once daily to self-renew and remain as stem cells, 2) leave the niche and differentiate into progenitor cells that divide more rapidly (twice daily) before maturing into cells responsible for nutrient absorption, or 3) directly convert into specialised cell types with protective, sentinel functions.
These quantitative insights emerged from the interdisciplinary collaboration between Isidora Banjac and Cecilia Lövkvist, a computational scientist and senior researcher in the team. To reach these conclusions, Isidora dedicated weeks to microscopy, imaging samples from various mouse models, and quantifying the resulting images to map cell divisions and differentiation events in the crypt. This work served as the foundation for a mathematical model that explained the biological observations. This highlights the importance of interdisciplinary research in modern science, where wet lab-based quantitative data are integrated with mathematical modelling.
“In order to really appreciate the complexity and the depth of biological data, it is essential to work across fields and bring together individuals with a computational and wet lab background. Addressing questions like this and fostering the interaction at the beginning of a project ensures that you capture the right parameters and thereby generate data of the highest possible value when you get to do the subsequent analysis,” said Professor Kim Bak Jensen.
The findings of the paper provide crucial insights into the functioning of a healthy intestine and how it is maintained throughout a long life.
“Prior to this work, the field expected that there would be a secretory progenitor that would be dividing, but what we clearly show here, and this is actually aligned with a lot of the literature, is the fact that we don't have a progenitor that divides in the secretory lineage, but that the stem cells go on to differentiate directly into one of these different cell types,” said Professor Jensen.
These results establish an essential baseline for future research aimed at understanding diseased tissues and developing new therapies for intestinal disorders.
Read the paper.