Intestinal cellular heterogeneity and disease development revealed by single-cell technology

Abstract

The intestinal epithelium is responsible for food digestion and nutrient absorption and plays a critical role in hormone secretion, microorganism defense, and immune response. These functions depend on the integral single-layered intestinal epithelium, which shows diversified cell constitution and rapid self-renewal and presents powerful regeneration plasticity after injury. Derailment of homeostasis of the intestine epithelium leads to the development of diseases, most commonly including enteritis and colorectal cancer. Therefore, it is important to understand the cellular characterization of the intestinal epithelium at the molecular level and the mechanisms underlying its homeostatic maintenance. Single-cell technologies allow us to gain molecular insights at the single-cell level. In this review, we summarize the single-cell RNA sequencing applications to understand intestinal cell characteristics, spatiotemporal evolution, and intestinal disease development.

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

“…The epithelial lining of the lumen and the crypts (intestinal glands or crypt units) in the colon is composed of columnar absorptive cells (enterocytes, colonocytes), goblet (oligomucous) cells (GCs), regenerative cells/intestinal stem cells (ISCs) and the less-abundant enteroendocrine cells (EECs) [ 99 , 100 , 101 ]. In the organization of the colonic crypt, ISCs are located in the lowest parts, giving rise to transit-amplifying (TA) precursor cells, and finally to fully differentiated cells [ 99 ].…”

“…These phenomena underlie colorectal diseases, such as IBD, ulcerative colitis (UC) and CD [ 100 ]. The high heterogeneity of human colonic epithelial cells, together with an understanding of their functions and markers, have become possible by recent molecular techniques at the single-cell level [ 101 , 102 ].…”

“…TA cells are located above ISCs within the intestinal crypts [ 99 , 159 ] and are differentiated into five main epithelial cell types [ 160 ]. The cellular composition of the small and large intestinal epithelium is controlled by ISCs with phenotype leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) [ 101 ].…”

Stromal BMP signaling regulates mucin production in the large intestine via interleukin-1/17

“…The intestine is an important organ for food digestion, nutrient absorption, hormone secretion, immune regulation, and host defense ( 1 ). Its multiple functions are based on the cooperation between intestinal epithelium and mesenchyme.…”

“…In addition to the immune cells, the intestinal mesenchyme also contains stromal cells, such as the telocytes for Wnt activation and bone morphogenic protein (BMP) inhibition ( 2 , 3 ), Gli1 + cells for Wnt signals ( 4 ), and Pdgfra low /Cd34 + /Cd81 + cells for BMP antagonists ( 5 ). The signaling cross-talk between stromal cells and the epithelium is fundamental to the balance maintenance between intestinal stem cells (ISCs) and mature epithelial cells, the basics of intestinal homeostasis ( 1 ).…”