Intestinal Stem Cell Niche: The Extracellular Matrix and Cellular Components

Received Apr 5, 2017; Accepted Jul 4, 2017

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1. Introduction

The intestinal epithelium is a monolayer of cells covering the entire lumen of the gut that constitutes an important barrier against the external environment. Both small and large intestine share similar glandular crypt structure where intestinal stem cells (ISCs) reside. Crypts are formed by epithelial invaginations into the extracellular matrix (ECM), cushioned by supportive stromal cells. The ISCs, marked by the leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5), reside at the crypt base alongside their neighbouring Paneth cells [1]. The ISCs divide and give rise to daughter cells entering the transit-amplifying (TA) zone. The TA cells will then proliferate and migrate upwards towards the crypt-villus junction, where they terminally differentiate into all different cell types, including enterocytes, goblet cells, enteroendocrine cells, and tuft cells, before reaching the villus tip and being exfoliated into the lumen, with the exception of Paneth cells that will migrate downwards back to the stem cell zone. The whole ISC proliferation-differentiation journey from the base of the crypt to the villus tip lasts approximately 3–5 days [1–3].

ISCs in the crypt base are maintained by their surrounding niche for precise regulation of self-renewal and differentiation under homeostasis. The ISC niche can be categorised fundamentally into two major components: the “physical” niche and the “cellular” niche. The physical niche refers to the ECM, which comprises an intricate network of fibrous structural proteins (proteoglycans and glycoproteins) that act as scaffolding to maintain the three-dimensional architecture of the intestine. Examples of ECM components surrounding the intestinal crypts include fibronectins, laminin isoforms, collagens, and glycosaminoglycans (GAGs) [4–11]. The cellular niche refers to the stromal microenvironment that comprises all the resident cells embedded within the ECM. These include pericryptal myofibroblasts, fibroblasts, endothelial cells, pericytes, immune cells, neural cells, and smooth muscle cells, which secrete a wide range of matrix components and growth factors for...