1: Reconstruction of the Human Colon Epithelium In Vivo
Science of the Month - April 2018
CELL STEM CELL
22 (2):171-+; 10.1016/j.stem.2017.11.012 FEB 1 2018
Sugimoto Shinya, Ohta Yuki, Fujii Masayuki, Matano Mami, Shimokawa Mariko, Nanki Kosaku, Date Shoichi, Nishikori Shingo, Nakazato Yoshihiro, Nakamura Tetsuya, Kanai Takanori, Sato Toshiro
Tissue stem cells have been demonstrated by the long-term self-renewal of a single extracted stem cell in a transplanted animal or culture dish. However, unlike blood cells, which are inherently dispersed, most epithelial cells die when isolated. Recently, "lineage tracing" was developed to observe the production of progeny from genetically marked cells without disrupting the tissue. Because this lineage tracing requires genetic engineering, it has only been applied in mice. In this study, we succeeded in lineage tracing of human tissue stem cells through the development of two technologies. First, using human colonic cells cultured ex vivo, we performed genome editing to visualize the progeny of LGR5 gene-expressing cells. Next, we established a transplantation technique to strip the mouse colonic epithelium and replace it with human colonic epithelial cells. These technologies enabled us to successfully observe the long-term self-replication and diverse epithelial cell differentiation of LGR5-expressing cells in a tissue environment. Interestingly, unlike the rapidly proliferating mouse colonic stem cells, human colonic stem cells exhibited slow proliferation. Colonic stem cells are known to accumulate mutations with each division, suggesting a possible link between proliferation speed and colon carcinogenesis. Furthermore, this technology enables the study of human colonic stem cells in the intestinal environment, and its application to a wide range of research is anticipated.
(Toshiro Sato, 76th class, Gastroenterology; Shinya Sugimoto, 88th class)