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Publication : Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

First Author  Kim J Year  2023
Journal  Sci Adv Volume  9
Issue  47 Pages  eadi8454
PubMed ID  38000027 Mgi Jnum  J:358262
Mgi Id  MGI:7563540 Doi  10.1126/sciadv.adi8454
Citation  Kim J, et al. (2023) Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction. Sci Adv 9(47):eadi8454
abstractText  Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.
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