Intestinal stem cells in homeostasis and cancer

Abstract

Intestinal stem cell (ISC) population at crypts base displays extraordinary capability for organized renewal and regeneration of intestinal epithelium. Complex interplay among stem cells, its progeny and niche balances between selfrenewal and differentiation to maintain intestinal homeostasis. Involvement of various interactions to regulate intestinal epithelium rapid renewal, presents with high risk of developing cancer. Intestinal stem cells (ISCs) biology and cancer development is closely related in various aspects. Studies have shown, ISCs as the cells of origin for majority of intestinal cancer where signaling pathways regulating ISC are often deregulated, giving rise to cancer stem cell (CSC). Moreover, intestinal cancers are shown to maintain cellular hierarchy similar to intestinal epithelium with presence of CSC at apex. CSCs are cell subpopulation with ISC like features involved in tumor genesis. Here we present common and different features of ISC and CSC with special emphasis on differential regulation of Wnt, Notch and BMP signaling pathways in both stem cell populations. Recent identification of both ISC and CSC markers along with technological development to track stem cell lineage and endogenous activity in vivo with possibility to generate ex vivo intestinal organoids, has broaden our understanding regarding ISC driven intestinal epithelium homeostasis, repair and cancer. Basic understanding of intestinal stem cell biology and its role in carcinogenesis opens up exciting opportunity to develop stem cell based therapeutics for cancer treatment.