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Willet, S. G., Lewis, M. A., & Miao, Z.-F. (2018). Regenerative proliferation of differentiated cells by mtorc1-dependent paligenosis. The EMBO Journal, 37(7), e98311. Added by: Dr. Enrique Feoli (25/05/2023, 13:53) Last edited by: Dr. Enrique Feoli (23/09/2023, 12:40) |
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| Resource type: Journal Article DOI: https://doi.org/10.15252/embj.201798311 BibTeX citation key: Willet2018 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Cell plasticity Creators: Lewis, Miao, Willet Collection: The EMBO Journal |
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| Abstract |
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In 1900, Adami speculated that a sequence of context-independent energetic and structural changes governed the reversion of differentiated cells to a proliferative, regenerative state. Accordingly, we show here that differentiated cells in diverse organs become proliferative via a shared program. Metaplasia-inducing injury caused both gastric chief and pancreatic acinar cells to decrease mTORC1 activity and massively upregulate lysosomes/autophagosomes; then increase damage associated metaplastic genes such as Sox9; and finally reactivate mTORC1 and re-enter the cell cycle. Blocking mTORC1 permitted autophagy and metaplastic gene induction but blocked cell cycle re-entry at S-phase. In kidney and liver regeneration and in human gastric metaplasia, mTORC1 also correlated with proliferation. In lysosome-defective Gnptab−/− mice, both metaplasia-associated gene expression changes and mTORC1-mediated proliferation were deficient in pancreas and stomach. Our findings indicate differentiated cells become proliferative using a sequential program with intervening checkpoints: (i) differentiated cell structure degradation; (ii) metaplasia- or progenitor-associated gene induction; (iii) cell cycle re-entry. We propose this program, which we term “paligenosis”, is a fundamental process, like apoptosis, available to differentiated cells to fuel regeneration following injury.
Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Notes |
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Upon acute injury, differentiated cells in diverse organs are re-activated via a common program controlling autodegradative pathways, increased expression of damage-associated metaplastic genes and cell cycle re-entry.
We recently identified Ifrd1 and Ddit4 as paligenosis-governing genes and proposed that paligenosis genes in general would be: (i) largely dispensable for normal development or proliferative activity; (ii) activated primarily during regeneration-inducing injury; and (iii) highly evolutionarily conserved. We argue here that ATF3 is a similar such gene required for paligenosis. It is upregulated early in paligenosis in multiple tissues, is known to be induced by injury, and is conserved from sea anemones to humans, and, in general, organisms null for ATF3 have phenotypes only after injury. Added by: Dr. Enrique Feoli Last edited by: Dr. Enrique Feoli |
| Paraphrases |
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Fundamental para comprender acción de AcP. RiBi como proceso que comsume la mayor dis ponibilidad de energía y es proceso fundamental en la paligenosis, por tal razón, daño tisular debe ser tratado fundamentalmente con suplementación de energía.
Added by: Dr. Enrique Feoli
(2023-09-23 12:25:14)
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