Proper function and repair of the digestive system are vital to most animals. Deciphering the mechanisms involved in these processes requires an atlas of gene expression and cell types. Here, we applied laser-capture microdissection (LCM) and RNA-seq to characterize the intestinal transcriptome of Schmidtea mediterranea, a planarian flatworm that can regenerate all organs, including the gut. We identified hundreds of genes with intestinal expression undetected by previous approaches. Systematic analyses revealed extensive conservation of digestive physiology and cell types with other animals, including humans. Furthermore, spatial LCM enabled us to uncover previously unappreciated regionalization of gene expression in the planarian intestine along the medio-lateral axis, especially among intestinal goblet cells. Finally, we identified two intestine-enriched transcription factors that specifically regulate regeneration (hedgehog signaling effector gli-1) or maintenance (RREB2) of goblet cells. Altogether, this work provides resources for further investigation of mechanisms involved in gastrointestinal function, repair and regeneration.
Keywords: digestive system; genetics; genomics; intestine; laser-capture microdissection; planarian; regeneration; regenerative medicine; stem cells.
The human body has a limited ability to regenerate and repair itself after major injuries. By contrast, flatworms – most notably planarians such as Schmidtea mediterranea – have exceptional regenerative abilities and can regrow large parts of their bodies. Regrowing body parts is a complex process involving the coordinated creation of many different types of cells, and thus an important first step in understanding tissue regeneration is to develop a detailed catalog of cell types in that tissue. Laser capture microdissection, or LCM for short, is a technology used to isolate and study subregions or even individual cells from within a tissue. This approach can help to identify different cell types and to examine what makes them unique. LCM can be used to create a detailed catalog of cells, their differences and the roles they perform. Forsthoefel et al. have now used LCM to study cells from the planarian digestive system. This approach found 1,800 genes that have high activity in cells from the gut and showed many similarities between planaria and humans. LCM made it possible to study these cells in a new level of detail, revealing several hundred new genes as well as new cell types. The study showed that regeneration and survival of cells known as goblet cells particularly depended on two genes, gli-1 and RREB2. Irreversible gut damage in humans can result from surgeries and conditions such as acid reflux. Other animals are able to repair and regenerate the gut more successfully. Techniques like LCM can help researchers to understand the differences between humans and other species. In time, these insights may lead to technologies and therapies that can improve our own abilities to heal following injuries.
© 2020, Forsthoefel et al.