Highlights d Dedicated genes govern paligenosis, a conserved cellular regeneration program d DDIT4 first blocks mTORC1, inducing massive autophagy to downscale the cell d p53 activation continues mTORC1 suppression to maintain cell quiescence d IFRD1 suppresses p53 to reinduce mTORC1 and license progression into the cell cycle
Highlights d AMPK promotes generation of acid-secreting parietal cells from stem cells d Metformin slows progenitor cell proliferation by activating AMPK and KLF4 d Metformin induces parietal cell maturation by activating AMPK and PGC1a
We introduce the differing methods for culturing healthy gastric tissue from adult tissues, pluripotent stem cells or gastric cancer tissue. We also discuss the promise these systems have for preclinical drug screens and highlight the applications of organoids for precision medicine.The stomach is a complex and physiologically necessary organ, yet large differences in physiology between mouse and human stomachs have impeded translation of physiological discoveries and drug screens performed using murine gastric tissues. Gastric cancer (GC) is a global health threat, with a high mortality rate and limited treatment options. The heterogeneous nature of GC makes it poorly suited for current "one size fits all" standard treatments. In this review, we discuss the rapidly evolving field of gastric organoids, with a focus on studies expanding cultures from primary human tissues and describing the benefits of mouse organoid models. We introduce the differing methods for culturing healthy gastric tissue from adult tissues or pluripotent stem cells, discuss the promise these systems have for preclinical drug screens, and highlight applications of organoids for precision medicine. Finally, we discuss the limitations of these models and look to the future to present potential ways gastric organoids will advance treatment options for patients with GC.
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