Reserve Stem Cells in Intestinal Homeostasis and Injury Eric D. Bankaitis, Andrew Ha, Calvin J. Kuo, Scott T. Magness  Gastroenterology  Volume 155, Issue 5, Pages 1348-1361 (November 2018) DOI: 10.1053/j.gastro.2018.08.016 Copyright © 2018 AGA Institute Terms and Conditions

Figure 1 Role of crypt-localized cells in epithelial homeostasis and injury-induced regeneration. (A) Homeostatic renewal of the intestinal epithelium (comprising ISCs, transit-amplifying progenitors, absorptive enterocytes, Paneth, goblet, enteroendocrine, and tuft cells) is mediated by aISCs in the crypt base. A rare pool of ISCs located near the +4 position is maintained in a quiescent state (+4 ISC), making only minimal contributions to the homeostatic maintenance of aISC and renewal of differentiated lineages. (B) During injury-induced regeneration, when aISCs are compromised or lost, rISCs become a primary cell source that mediates regeneration. Plastic non-ISC cell types can also contribute to regenerating epithelial tissue (blue arrows), presumably through the generation of an aISC intermediate. The +4 position is an approximation, referring to a region of the crypt from +4 to +7 nuclear positions, counted upward from the bottom-most nucleus in the crypt base. Gastroenterology 2018 155, 1348-1361DOI: (10.1053/j.gastro.2018.08.016) Copyright © 2018 AGA Institute Terms and Conditions

Figure 2 Models for conversion between aISCs and rISCs. (A) Canonical Wnt signaling mediates self-renewal of the aISC pool, which is the predominant source of all differentiated lineages. Conversion between aISCs and rISCs can occur, but is rarely observed under normal physiologic conditions. (B) When aISCs are selectively lost after injury, rISCs become activated and convert to aISCs via mechanisms that are currently unclear. (C) Epithelial repair is achieved as the aISC pool is replenished by rISCs, and regeneration of the full complement of epithelial cell types is completed. The rISC pool at this stage is presumably re-established, though this has not been formally tested. NOTE. Transit-amplifying populations are not shown in this diagram. Gastroenterology 2018 155, 1348-1361DOI: (10.1053/j.gastro.2018.08.016) Copyright © 2018 AGA Institute Terms and Conditions

Figure 3 Expression patterns of biomarkers commonly associated with rISCs. Originally reported biomarker specificity is indicated in dark blue. Marker expression patterns reported afterward are indicated in light blue. It is not clear whether and how gene expression patterns are altered, especially within short time periods, during injury (∗). Gastroenterology 2018 155, 1348-1361DOI: (10.1053/j.gastro.2018.08.016) Copyright © 2018 AGA Institute Terms and Conditions