JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

Publication date: Available online 21 December 2017 Source:Stem Cell Reports Author(s): Camilla A. Richmond, Hannah Rickner, Manasvi S. Shah, Tracy Ediger, Luke Deary, Fanny Zhou, Alessio Tovaglieri, Diana L. Carlone, David T. Breault The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs) and slowly cycling, reserve ISCs (r-ISCs). Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response. Graphical abstract Teaser Richmond et al. demonstrate that, following intestinal inflammatory injury, reserve intestinal stem cells (r-ISCs) exit quiescence and con...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research