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

Distinct signaling signatures drive compensatory proliferation via S-phase acceleration DOI Creative Commons
Carlo Crucianelli, Janhvi Jaiswal,

Ananthakrishnan Vijayakumar Maya

et al.

PLoS Genetics, Journal Year: 2022, Volume and Issue: 18(12), P. e1010516 - e1010516

Published: Dec. 15, 2022

Regeneration relies on cell proliferation to restore damaged tissues. Multiple signaling pathways activated by local or paracrine cues have been identified promote regenerative proliferation. How different types of tissue damage may activate distinct and how these differences converge is less well defined. To better understand proliferative signals are integrated during regeneration, we investigate models compensatory in Drosophila imaginal discs. We find that associated with a unique cycle profile, which characterized short G1 G2 phases and, surprisingly, acceleration the S-phase. S-phase can be induced two signatures, aligning inflammatory non-inflammatory damage. Specifically, non-autonomous activation JAK/STAT Myc response damage, Ras/ERK Hippo/Yki elevated death, accelerated nucleotide incorporation This previously unappreciated convergence damaging insults same program reconciles previous conflicting observations regeneration tumor models.

Language: Английский

Citations

7
Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration DOI
Augusto Ortega Granillo,

Daniel Zamora,

Robert R. Schnittker

et al.

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

Published: March 31, 2024

Summary Injury is a common occurrence in the life of organisms. Because extent damage cannot be predicted, injured organisms must determine how much tissue needs to restored. It known that amputation position determines regeneration speed amputated appendages regeneration-competent animals. Yet, it not clear positional information conveyed during regeneration. Here, we investigated dynamics regenerating caudal fins African killifish ( Nothobranchius furzeri ). We report position-specific, differential modulation spatial distribution, duration, and magnitude proliferation. Regenerating profiled by single cell RNA sequencing identified Transient Regeneration-Activated Cell State (TRACS) amplified match given position. located this TRACS basal epidermis found them express components modifiers extracellular matrix (ECM). propose role for these cells transducing blastema remodeling ECM. Highlights Amputation changes tissue-wide proliferation response Transcriptional compartmentalization relative injury type Regeneration deploys States Prediction: transduced ECM

Language: Английский

Citations

1
Inonotus obliquus aqueous extract inhibits intestinal inflammation and insulin metabolism defects in Drosophila DOI

Shichao Yu,

Zhixian Lai,

Hongmei Xue

et al.

Toxicology Mechanisms and Methods, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 15

Published: June 14, 2024

In biomedical research, the fruit fly (

Language: Английский

Citations

1
Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity DOI Creative Commons
Jacob W Klemm,

Chloe Van Hazel,

Robin E Harris

et al.

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

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 effective 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

1
Cloning of suppressor of cytokine signaling 7 from silkworm (Bombyx mori) and its response to the infection of Bombyx mori nucleopolyhedrovirus DOI
Qian Wang, Miao Cui, Cong Zhang

et al.

Archives of Insect Biochemistry and Physiology, Journal Year: 2023, Volume and Issue: 115(1)

Published: Nov. 28, 2023

Abstract Suppressors of cytokine signaling (SOCS) play important roles in the regulation growth, development, and immunity eukaryotic organisms. SOCS7 is an member SOCS family, but its physiological pathological functions remain largely unknown invertebrates including insects. Here, we first report cloning a gene from domesticated silkworm ( Bombyx mori ), named BmSOCS7 . We have characterized expression profiles varieties susceptible or resistant to infection nucleopolyhedrovirus (BmNPV) using real‐time fluorescence quantitative PCR. expresses highly embryogenesis lowly metamorphosis silkworms does opposite contrast silkworms. Its at very low level fat body relatively high ones. BmNPV inoculation induces transient downregulation then general upregulation BmN cells, while it midgut, hemolymph with more pronounced effect than ones prominent midgut. Together, our work reveals that may be strategy for anti‐BmNPV immune response, mainly function rather midgut participate process.

Language: Английский

Citations

1
Niacin alleviates extracellular matrix deposition in ethanol + CCl4-induced liver fibrosis through the HSP90/JAK1/STAT3 axis DOI

Yanping Fan,

Meilan Xue,

Tianhu Shan

et al.

Food Bioscience, Journal Year: 2023, Volume and Issue: 57, P. 103454 - 103454

Published: Dec. 10, 2023

Language: Английский

Citations

1
Oncogenic signaling in the adult Drosophila prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation. DOI Creative Commons

Samuel Jaimian Church,

Ajai J. Pulianmackal,

Joseph A. Dixon

et al.

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

Published: May 12, 2024

Abstract Drosophila models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many these use the proliferating tissues larval stages development, when highly mitotically active, or stem cells abundant. Fewer adult animals to initiate tumor formation many largely terminally differentiated postmitotic. The accessory glands prostate-like a model some aspects prostate using this tissue has been explored. In model, oncogenic was induced during proliferative stage gland raising question how activity would impact postmitotic tissue. Here, we show leads activation pro-tumorigenic program, similar observed mitotic tissues, but absence proliferation. Oncogenic hyperplasia with nuclear anaplasia aneuploidy through endoreduplication, which increases polyploidy occasionally results non-mitotic neoplastic-like extrusions. We compare gene expression changes our endocycling cancer by chemotherapy, potentially mediate recurrence after treatment. Similar pathways activated cells, suggesting provide useful progression do not involve cellular

Language: Английский

Citations

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

Chloe Van Hazel,

Robin E Harris

et al.

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

Published: July 26, 2024

Abstract 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
PDK-1/S6K and mTORC1 bypass systemic growth restrictions to promote regeneration DOI Creative Commons

Ananthakrishnan Vijayakumar Maya,

Liyne Nogay,

Lara Heckmann

et al.

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

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.

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

Published: Aug. 9, 2024

Abstract Background Hemorrhagic fever with renal syndrome (HFRS), a life-threatening zoonosis caused by hantavirus, poses significant mortality risks and lacks specific treatments. This study aimed to delineate the transcriptomic alterations during recovery phases of HFRS. Methods RNA sequencing was employed analyze in peripheral blood mononuclear cells from HFRS patients across oliguric phase (OP), diuretic (DP), convalescent (CP). Twelve differentially expressed genes (DEGs) were validated using quantitative real-time PCR larger sample sets. Results Our analysis revealed pronounced differences between DP OP, 38 DEGs showing consistent expression changes all three phases. Notably, immune checkpoint like CD83 NR4A1 demonstrated monotonic increase, contrast decrease observed antiviral immunomodulatory genes, including IFI27 RNASE2. Furthermore, this research elucidates sustained attenuation responses phases, alongside an upregulation pathways related tissue repair regeneration. Conclusion reveals shifts HFRS, illuminating key that may serve as biomarkers for disease progression recovery.

Language: Английский

Citations

0