ATF3 and colitis: Although genetic depletion of Paneth cells in vivo results in the concomitant loss of Lgr5+ stem cells (45), we reason that ATF3 is primarily targeting stem cell homeostasis and regeneration, but not Paneth cells in the niche, as organoid transplantation effectively ameliorates colitis and restores total crypt numbers in DSS-treated ATF3−/− mice.