A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration DOI Creative Commons
Jeffrey F. Quinn,

M Lee,

Chloe Van Hazel

et al.

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

Published: Nov. 3, 2024

Abstract Tissue regeneration requires the directed activity of numerous genes, which are often reused from development. Although identities many key factors have been established, how their expression is activated and subsequently coordinated over regenerative time remains unclear. One highly conserved signal central to diverse examples stress MAP kinase JNK. In Drosophila , damage-induced JNK signaling promotes multiple genes that direct proliferation, growth changes in cellular identity. However, these targets selectively upregulated context injury, expressed specific patterns responsible for repair unknown. Our work previously characterized Damage-Responsive, Maturity-Silenced (DRMS) enhancers; regulatory elements directly by promote gene expression. Here we investigated damage-responsive (DR) module enhancers engaged, finding cell death entirely dispensable activation. We identify JAK/STAT as an additional input into DR downstream JNK, acts broaden enhancer wound periphery where levels insufficient alone. Finally, demonstrate a distinct threshold level exists must be achieved activate via enhancers, which, alongside JAK/STAT, results temporally spatially appropriate necessary regeneration. Author Summary Wound healing require activation whose carefully division, identity organ development restoration tissue integrity patterning. The imaginal disc well-established model used better understand spatiotemporal control reparative response damage discs primarily mediated thorough pathway, but leads diversity occurs around not well understood. discrete genomic regions called Damage-Responsive respond program. show behavior depends on they integrate both its immediate target establish proper regionality expression, promoting spread wound. These findings improve our understanding patterning established damage.

Language: Английский

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration. DOI Creative Commons
Augusto Ortega Granillo,

Daniel Zamora,

Robert R. Schnittker

et al.

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110737 - 110737

Published: Aug. 23, 2024

Highlights•Amputation position changes tissue-wide proliferation response•Regeneration deploys transient regeneration-activated cell states•Sqstm1 slows down regenerative outgrowth in distal injuries•Prediction: positional information is transduced by ECM during regenerationSummaryInjury common the life of organisms. Because extent damage cannot be predicted, injured organisms must determine how much tissue needs to restored. Although it known that amputation affects regeneration speed appendages, mechanisms conveying remain unclear. We investigated dynamics regenerating caudal fins African killifish (Nothobranchius furzeri) and found position-specific, differential spatial distribution modulation, persistence, magnitude proliferation. Single-cell RNA sequencing revealed a state (TRACS) basal epidermis amplified match given expresses components modifiers extracellular matrix (ECM). Notably, CRISPR-Cas9-mediated deletion modifier sequestosome 1 (sqstm1) increased capacity injuries, suggesting growth rate can uncoupled from position. propose TRACS transduce blastema remodeling ECM.Graphical abstract

Language: Английский

Citations

0
Transcriptomic analysis reveals key molecular signatures across recovery phases of hemorrhagic fever with renal syndrome DOI Creative Commons
Yuanyuan Hu, Chao Wu,

T. Li

et al.

BMC Medical Genomics, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 11, 2024

Language: Английский

Citations

0
Systematic analysis of functional implications of fibrosis in pan-cancer DOI
Yao Long,

Lianpo Liu,

Hanlin Wang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 25, 2024

Abstract The common pathogenic mechanisms and molecular pathways of fibrosis tumors remain unclear. We aimed to conduct in-depth analysis feature genes role from a pan-cancer perspective identify potential therapeutic targets for idiopathic pulmonary cancers. downloaded mRNA expression, copy number alterations, DNA methylation data 33 cancers Cancer Genome Atlas (TCGA). Clinical mutation were obtained the UCSC Xena database. frequencies fibrosis-feature-related (FRGs) in TCGA database examined. Protein expression levels analysed using Proteomics Tumor Analysis Consortium. Gene Set Variation Enrichment algorithms used. Most FRGs differentially expressed owing somatic cell alterations methylation. established index (FPI), most cancers, FPI was lower than that normal tissues correlated with subtypes clinical features. negatively multiple metabolic immune function but positively several important tumor features or pathways. prognosis different tumors, despite finding heterogeneity. Fibrotic have excellent diagnostic prognostic capabilities various This may help predict responses immunotherapy.

Language: Английский

Citations

0
Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity DOI Open Access
Jacob W Klemm,

Chloe Van Hazel,

Robin E Harris

et al.

Published: Sept. 30, 2024

Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of how it impacts surrounding healthy tissue – an essential consideration when developing methods to treat such injuries has been limited by lack robust genetically tractable models. Our lab previously established method study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed unique phenomenon whereby cells at distance from injury upregulate caspase activity process called Necrosis-induced Apoptosis (NiA) that vital regeneration. Here we have further investigated this phenomenon, showing NiA predominantly associated with highly regenerative pouch region shaped genetic factors present presumptive hinge. Furthermore, find proportion fail undergo apoptosis, instead surviving effector activation persist within stimulate reparative proliferation late This relies on initiator Dronc, occurs independent JNK, ROS or mitogens characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal new means non-apoptotic Dronc signaling promotes response necrotic damage.

Language: Английский

Citations

0
A threshold level of JNK activates damage-responsive enhancers via JAK/STAT to promote tissue regeneration DOI Creative Commons
Jeffrey F. Quinn,

M Lee,

Chloe Van Hazel

et al.

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

Published: Nov. 3, 2024

Abstract Tissue regeneration requires the directed activity of numerous genes, which are often reused from development. Although identities many key factors have been established, how their expression is activated and subsequently coordinated over regenerative time remains unclear. One highly conserved signal central to diverse examples stress MAP kinase JNK. In Drosophila , damage-induced JNK signaling promotes multiple genes that direct proliferation, growth changes in cellular identity. However, these targets selectively upregulated context injury, expressed specific patterns responsible for repair unknown. Our work previously characterized Damage-Responsive, Maturity-Silenced (DRMS) enhancers; regulatory elements directly by promote gene expression. Here we investigated damage-responsive (DR) module enhancers engaged, finding cell death entirely dispensable activation. We identify JAK/STAT as an additional input into DR downstream JNK, acts broaden enhancer wound periphery where levels insufficient alone. Finally, demonstrate a distinct threshold level exists must be achieved activate via enhancers, which, alongside JAK/STAT, results temporally spatially appropriate necessary regeneration. Author Summary Wound healing require activation whose carefully division, identity organ development restoration tissue integrity patterning. The imaginal disc well-established model used better understand spatiotemporal control reparative response damage discs primarily mediated thorough pathway, but leads diversity occurs around not well understood. discrete genomic regions called Damage-Responsive respond program. show behavior depends on they integrate both its immediate target establish proper regionality expression, promoting spread wound. These findings improve our understanding patterning established damage.

Language: Английский

Citations

0