Recent Advances in Intestinal Stem Cells

Abstract

Purpose of review The intestine is a dynamic organ with rapid stem cell division generating epithelial cells that mature and apoptose in 3–5 days. Rapid turnover maintains the epithelial barrier and homeostasis. Current insights on intestinal stem cells (ISCs) and their regulation are discussed here. Recent findings The Lgr5+ ISCs maintain intestinal homeostasis by dividing asymmetrically, but also divide symmetrically to extinguish or replace ISCs. Following radiation or mucosal injury, reserve BMI1+ ISCs as well as other crypt cells can de-differentiate into Lgr5+ ISCs. ISC niche cells, including Paneth, immune and myofibroblast cells secrete factors that regulate ISC proliferation. Finally, several studies indicate that the microbiome metabolites regulate ISC growth. Summary ISC cells can be plastic and integrate a complexity of environmental/niche cues to trigger or suppress proliferation as needed.

Control of Intestinal Epithelial Proliferation and Differentiation: The Microbiome, Enteroendocrine L Cells, Telocytes, Enteric Nerves, and GLP, Too

“…For most, a fully formed adult organism can arise from a single cell that contains the information, combined with environmental cues, necessary to orchestrate the near-miraculous series of controlled and timed cell divisions, migrations, differentiations, maturations, connections, and cell death needed for overall growth and maturation of the organism. The ability for cells to proliferate, divide, mature, and differentiate is retained in adults, albeit in small, defined regions termed the "stem cell niche", where many of the factors controlling embryonic growth, proliferation, and differentiation are retained [1][2][3][4]. In most organs, proliferation mostly occurs after injury, such as in the liver, which has a remarkable ability to regenerate [5].…”

The Role of Long Noncoding RNAs in Intestinal Health and Diseases: A Focus on the Intestinal Barrier

“…Intestinal stem cells are considered the source of all intestinal cells and are responsible for epithelial renewal in physiological conditions and intestinal regeneration in response to injury [49]. Stem cells divide and produce transit-amplifying cells (TA cells), which then differentiate downward into Paneth cells and upward into goblet cells, enteroendocrine cells, and intestinal absorptive cells [50]. Paneth cells are located in the crypt of the small intestine, and they can produce antimicrobial peptides and immunomodulatory proteins to regulate the composition of intestinal bacteria [51].…”

Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage

“…In fact, most proliferative cells rely on aerobic glycolysis (Warburg effect) in contrast to differentiated cells which rely mainly on oxidative phosphorylation. There are two types of Lgr5 + ISCs, the quiescent cells and the proliferative that will give rise to progenitor cells that are being differentiated [ 89 ]. For example, the proliferative Lgr5 + SCs, in order to proliferate, are limiting OXPHOS by downregulating the mitochondrial pyruvate carrier (MPC), which prevent cells from achieving an efficient pyruvate uptake into the mitochondria [ 90 ] (Fig.…”