Tracing the origin of adult intestinal stem cells
Jordi Guiu, Biotech Research & Innovation Centre – University of Copenhagen
Jordi Guiu did his PhD in Anna Bigas laboratory (IMIM and Pompeu Fabra University-Barcelona) were he focused on the genetic circuitry that controls the establishment of hematopoietic stem cells during development. Then he joined Kim B. Jensen lab (Copenhagen University) as a postdoc, were he obtained a Marie Curie fellowship. His current research is focused on the specification of intestinal stem cells during development using fate mapping technologies, state of the art imaging, biophysical modeling and a plethora of sequencing techniques.
The adult small intestine is compartmentalized into villi and crypts containing post-mitotic differentiated and proliferative cells respectively. Intestinal stem cells (ISCs) located at the bottom of crypts express markers such as Lgr5 and fuel the constant replenishment of the intestinal epithelium. Importantly, the cellular origin of adult ISCs remains unknown. Prior to birth the immature fetal intestine is structurally simpler than the adult intestine. It is characterized by villi separated by a continuous region composed of proliferative intervillus cells; crypts have not formed and there is no evidence of a stem cell niche. Interestingly, intervillus cells located within the region between villi express the adult ISC marker Lgr5. Fate mapping studies have inferred the notion that fetal Lgr5 expressing cells are unique and specialized precursors for the adult ISCs. Using unbiased quantitative lineage-tracing approaches, biophysical modeling and intestinal transplantation experiments, we now demonstrate that in the fetal epithelium on-going tissue morphogenesis leads to a dynamic exchange of cells between the villi and intervillus regions and that all cells have got the potential to contribute to the adult stem cells. Moreover, we present exciting data outlining the mechanism for tissue development based on 3D imaging and live microscopy. Our results demonstrate that large-scale tissue remodeling and cell fate specification are intertwined processes. Moreover, these findings provide a direct link between the observed plasticity and cellular reprogramming of differentiating cells in adult tissue following damage, revealing that stem cell identity is an induced rather than a hardwired property.