Mutual repression between JNK/AP-1 and JAK/STAT stratifies senescent and proliferative cell behaviors during tissue regeneration

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(5), P. e3001665 - e3001665

Published: May 30, 2023

Epithelial repair relies on the activation of stress signaling pathways to coordinate tissue repair. Their deregulation is implicated in chronic wound and cancer pathologies. Using TNF-α/Eiger-mediated inflammatory damage Drosophila imaginal discs, we investigate how spatial patterns behaviors arise. We find that Eiger expression, which drives JNK/AP-1 signaling, transiently arrests proliferation cells center associated with a senescence program. This includes production mitogenic ligands Upd family, allows JNK/AP-1-signaling act as paracrine organizers regeneration. Surprisingly, cell-autonomously suppress via Ptp61F Socs36E, both negative regulators JAK/STAT signaling. As suppressed at damage, compensatory occurs by periphery. Mathematical modelling suggests cell-autonomous mutual repression between core regulatory network essential spatially separate into bistable domains distinct cellular tasks. Such stratification for proper repair, coactivation same creates conflicting signals cell cycle progression, leading excess apoptosis senescently stalled organize field. Finally, demonstrate separation senescent proliferative not only upon but also Ras V12 , scrib tumors. Revealing this previously uncharacterized JNK/AP-1, JAK/STAT, has important implications our conceptual understanding pathologies, tumor microenvironments.

Language: Английский

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Inter-organ communication during tissue regeneration

Development, Journal Year: 2023, Volume and Issue: 150(23)

Published: Nov. 27, 2023

ABSTRACT Tissue regeneration is not simply a local repair event occurring in isolation from the distant, uninjured parts of body. Rather, evidence indicates that whole-animal process involving coordinated interactions between different organ systems. Here, we review recent studies reveal how remote tissues and systems respond to engage regeneration. We also discuss need for toolkits technological advancements uncover dissect communication during

Language: Английский

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Variations in cell plasticity and proliferation underlie distinct modes of regeneration along the antero-posterior axis in the annelid Platynereis

Development, Journal Year: 2024, Volume and Issue: 151(20)

Published: July 2, 2024

ABSTRACT The capacity to regenerate lost tissues varies significantly among animals. Some phyla, such as the annelids, display substantial regenerating abilities, although little is known about cellular mechanisms underlying process. To precisely determine origin, plasticity and fate of cells participating in blastema formation posterior end regeneration after amputation annelid Platynereis dumerilii, we developed specific tools track different cell populations. Using these tools, find that partly promoted by a population proliferative gut whose regenerative potential function their position along antero-posterior axis worm. Gut progenitors from anterior differentiated are lineage restricted, whereas less more much plastic. However, they unable stem responsible for growth worms. Those local deriving present segment abutting plane, most cells. Our results favour hybrid flexible model relying on degrees plasticity.

Language: Английский

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Coordination of cell cycle and morphogenesis during organ formation

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Jan. 26, 2024

Organ formation requires precise regulation of cell cycle and morphogenetic events. Using the Drosophila embryonic salivary gland (SG) as a model, we uncover role SP1/KLF transcription factor Huckebein (Hkb) in coordinating morphogenesis. The hkb mutant SG exhibits defects invagination positioning organ size due to abnormal death cells. Normal development involves distal-to-proximal progression endoreplication (endocycle), whereas cells undergo division, leading death. Hkb represses expression key pro-apoptotic genes SG. Knockdown cyclin E or cyclin-dependent kinase 1, overexpression fizzy-related rescues most observed These results indicate that plays critical controlling by regulating effectors ensure proper formation.

Language: Английский

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Antero-posterior gradients of cell plasticity and proliferation modulate posterior regeneration in the annelidPlatynereis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 12, 2023

Abstract Regenerative abilities are extremely variable among animals and may be substantial in some phyla, such as the annelids. So far, cellular mechanisms underlying regeneration annelids remain elusive. To precisely determine origin(s), plasticity fate of cells participating blastema formation during posterior annelid Platynereis dumerilii , we developed specific tools to track proliferative well gut epithelial cells. We showed that two populations progenitors at play that, them, from differentiated tissues lineage-restricted. Strikingly, less more much plastic can produce ectodermal mesodermal derivatives, addition However, their is de facto limited exemplified by inability regenerate stem responsible for constant growth worms. evidenced those local origin ( i.e. segment abutting amputation plan) most Our results favour a hybrid flexible model relying on gradient cell along antero-posterior axis animal.

Language: Английский

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PDK-1/S6K and mTORC1 bypass systemic growth restrictions to promote regeneration

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 6, 2024

Abstract Tissue damage and inflammation trigger systemic signals that induce catabolic breakdown nutrient release in distant organs, a process well-characterized the context of tumor cachexia. While mechanisms allowing tumors to circumvent these growth restrictions are known, physiological processes overcome inflammation-induced support tissue repair regeneration remain largely unexplored. In our study, we use model developing Drosophila imaginal discs dissect key metabolic signaling adaptations help restrictions. Our findings reveal unique strategy used by rapidly proliferating cells regenerating domain. Instead relying on conventional Insulin-PI3K-Akt pathway, utilize JAK/STAT-PDK1-S6K axis. This adaptation facilitates sustained protein synthesis cellular despite catabolism associated with low insulin signaling. Specifically, find fat body is driven insulin-binding factor Impl2, which expressed at site inflammatory damage. Notably, regenerative proliferation also supported mTORC1 activity upregulation amino acid transporters These align specific metabolite signature hemolymph, revealing specialized program meets demands fast-proliferating cells. work provides insight into how tissues rewire pathways adapt their coordinate conserved provision response. have important implications for understanding human diseases such as chronic wounds cancer.

Language: Английский

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Coordination of cell cycle and morphogenesis during organ formation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 21, 2023

Abstract Organ formation requires precise regulation of cell cycle and morphogenetic events. Using the Drosophila embryonic salivary gland (SG) as a model, we uncover role SP1/KLF transcription factor Huckebein (Hkb) in coordinating morphogenesis. The hkb mutant SG exhibits defects invagination positioning organ size due to abnormal death cells. Normal development involves distal-to-proximal progression endoreplication (endocycle), whereas cells undergo division, leading death. Hkb represses expression key pro-apoptotic genes SG. Knockdown cyclin E or cyclin-dependent kinase 1, overexpression fizzy-related rescues most observed These results indicate that plays critical controlling by regulating effectors ensure proper formation.

Language: Английский

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