Inhibition of TGF-beta signalling during zebrafish larval tail regeneration.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1259437 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33446914.fastq.gz | Fastqsanger.gz | |||
| SRR33446915.fastq.gz | Fastqsanger.gz | |||
| SRR33446916.fastq.gz | Fastqsanger.gz | |||
| SRR33446917.fastq.gz | Fastqsanger.gz | |||
| SRR33446918.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 48 |
Similar Datasets
Project description:This study investigates the role of TGF-beta signalling during tail regeneration in 72-96 hour old zebrafish. The inhibitor SB431542 was used to inhibit TGF-beta signalling with and without larval tail excision. Control larvae were treated with DMSO. The study identifies candidate differentially expressed genes (DEGs) after injury; TGF-beta-dependent, injury regulated DEGs; TGF-beta-dependent DEGs in the absence of injury; and TGF-beta-independent injury-dependent DEGs.
2025-05-16 | GSE296469 | GEO
Project description:Throughout their lifetime, fish maintain a high capacity for regenerating complex tissues after injury. We utilized a larval tail regeneration assay in the zebrafish Danio rerio, which serves as an ideal model of appendage regeneration due to its easy manipulation, relatively simple mixture of cell types, and superior imaging properties. Regeneration of the embryonic zebrafish tail requires development of a blastema, a mass of dedifferentiated cells capable of replacing lost tissue, a crucial step in all known examples of appendage regeneration. Using this model, we show that tail amputation triggers an obligate metabolic shift to promote glucose metabolism during early regeneration similar to the Warburg effect observed in tumor forming cells. Inhibition of glucose metabolism did not affect the overall health of the embryo but completely blocked the fin from regenerating after amputation due to the failure to form a functional blastema. We performed a time series of single cell RNA-sequencing on regenerating tails with and without inhibition of glucose metabolism. We demonstrated that metabolic reprogramming is required for sustained TGF-β signaling and blocking glucose metabolism largely mimicked inhibition of TGF-β receptors, both resulting in an aberrant blastema. Finally, we showed using genetic ablation of three possible metabolic pathways for glucose, that metabolic reprogramming is required to provide glucose specifically to the hexosamine biosynthetic pathway while neither glycolysis nor the pentose phosphate pathway were necessary for regeneration.
2021-09-07 | GSE145497 | GEO
Project description:X1 neoblasts (G2/S/M cells) were isolated by FACS from injury site-proximal tissue in a timeseries during head (anterior) and tail (posterior) regeneration in Schmidtea mediterranea 24 samples: 2 treatments (head versus tail regeneration), 3 timepoints (0,24,48,72 hours post amputation), 3 biological replicates each condition
2014-05-01 | E-GEOD-56178 | biostudies-arrayexpress
Project description:In this experiment, we show transcription profiling of the Xenopus tropicalis tadpole tail tissue regeneration following removal. The tail tissues include its spinal cord, notochord, muscle, and dorsal aorta. We characterized the early, intermediate, and late stages of Xenopus tropicalis tail regeneration using the Xenopus tropicalis Affymetrix genome array in biological replicate.
2010-10-01 | E-MEXP-2420 | biostudies-arrayexpress
Project description:In contrast to humans, many amphibians are able to rapidly and completely regenerate complex tissues, including complete appendages. Following tail amputation, Xenopus tropicalis tadpoles quickly regenerate muscle, spinal cord, cartilage, vasculature and skin, all properly patterned in three dimensions. To better understand the molecular basis of this regenerative competence, we performed a transcriptional analysis of regeneration using RNA-Seq. We profiled the transcriptome at 6 timepoints during tail regeneration, and used clustering analysis to identify biological processes that are prioritized during different transitions in the regeneration process. Our work expands significantly on previous expression analyses of tail regeneration. We are able to refine the windows during which many key biological signaling processes act, including embryonic patterning signals, immune responses, bioelectrical signaling and apoptosis. By including multiple timepoints within the first 24 hours post-amputation, we have also identified new processes that are highly prioritized early in regeneration, including axonogenesis, chemotaxis, and RNA metabolism. Our work provides a deep database for researchers interested in appendage regeneration, and highlights new avenues for further study.
2017-01-30 | GSE88975 | GEO
Project description:ATAC-Seq of Xenopus tail regeneration
| PRJNA575367 | ENA
Project description:The Mexican axolotl provides a powerful model to investigate mechanisms of tissue regeneration. A recent chemical screen found that HDAC inhibitor romidepsin, administered for only 1-minute post amputation (1 MPA), blocks axolotl tail regeneration. Here, we tested the potential for cobalt chloride (CoCl2), a chemical stabilizer of HIF1a and inducer of hypoxia, to rescue romidepsin-inhibition of tail regeneration. Tail regeneration was partially rescued when embryos with amputated tails were co-treated with romidepsin and CoCl2. However, extending the CoCl2 dosage window either inhibited regeneration (CoCl2:0-30 MPA) or was lethal (CoCl2:0-24 hours post amputation; HPA). CoCl2:0-30 MPA caused tissue damage, tissue loss, and cell death at the distal tail tip, and blocked regeneration. In contrast, CoCl2 treatment of non-amputated embryos or CoCl2:60-90 MPA treatment of amputated embryos did not affect wound healing or inhibit tail regeneration. To further investigate the contrasting effects of CoCl2, microarray analysis was performed to identify differentially expressed genes at 3 HPA. CoCl2-romidepsin:1 MPA treatment significantly increased the expression of transcription factors associated with appendage regeneration, while CoCl2:0-30 MPA significantly increased expression of hemoglobin and platelet-specific transcripts, consistent with hemorrhage and an impaired hemostatic response. Also, CoCl2:0-30 MPA significantly increased expression of hypoxia inducible genes, including genes that encode Hif1a interacting proteins and heat shock proteins (HSP); in contrast, genes encoding TGFB signaling components were significantly downregulated. Using additional chemical inhibitors of tail regeneration, we identified transcriptional responses associated with HSP90 activity and TGFB signaling. Notably, geldanamcin decreased transcription of matrix metalloproteinases and sustained muscle-specific gene expression, suggesting a role for HSP90 in regulating extracellular matrix remodeling and muscle dedifferentiation. Our study shows the power of using chemical tools to precisely identify temporal windows within which critical biological processes are enacted during tissue regeneration.
2021-01-01 | GSE150947 | GEO
Project description:Mammals possess limited regeneration capabilities, where the few examples of scarless healing tend to be restricted to early development. In light of this, it is of great interest to study animals that can faithfully regrow complete appendages, and uncover the biological properties that facilitate this process. Xenopus tropicalis tadpoles are excellent vertebrate models of regeneration, as they rapidly recover lost tails within just one week post amputation. Though we have some understanding of what pathways are required for tail regeneration, we have yet to systematically chronicle the regulatory events that coordinate this specialized response to injury. Here, we highlight a striking phenomenon in Xenopus regeneration, whereby nuclei within the fin epithelium of an amputated tail change shape in a dramatic and stereotyped manner during regeneration. We assess chromatin accessibility dynamics through ATAC-Seq of nine time points of regeneration, and find that large scale changes in chromatin state are highly correlated to changes in nuclear shape. To identify critical regulators of these chromatin dynamics, we describe and apply a machine learning method, PFBoost, which integrates information from motifs underlying dynamically accessible ATAC-Seq peaks and differentially expressed transcription factors from time-matched RNA-Seq data to predict chromatin state. To functionally evaluate PFBoost-predicted regeneration regulators, we developed an inducible CRISPRi system utilizing the FKBP derived destabilizing domain, and knockdown expression of these regulators during the early hours of regeneration. With this methodology, we identified and describe two novel regulators of regeneration, spib and chd8. We provide not only an abundant resource for chromatin dynamics in tail regeneration, but also chronicle an intriguing mechanism of regeneration regulation in the form of nuclear shape change and coordinate changes in chromatin state.
2020-01-31 | GSE138303 | GEO
Project description:Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 173 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 31) reproducibly inhibited tail regeneration, including multiple histone deacetylase inhibitors (HDACi). In particular, romidepsin potently inhibited tail regeneration when embryos were treated continuously for 7 days. Additional experiments revealed that romidepsin acts within a very narrow, post-injury window. Romidepsin treatment for only 1 minute post-amputation inhibited regeneration through the first 7 days, however after this time, regeneration commenced with variable outgrowth of tailfin tissue and abnormal patterning. Microarray analysis showed that romidepsin altered early, transcriptional responses at 3 and 6-hour post-amputation, especially targeting genes that function in the regulation of transcription, cell differentiation, cell proliferation, pattern specification, and tissue morphogenesis. Our results show that HDAC activity is required at the time of tail amputation to regulate the initial transcriptional response to injury and regeneration.
2019-01-31 | GSE118515 | GEO
Project description:Characterization of regeneration initiating cells during Xenopus laevis tail regeneration
| PRJNA1027815 | ENA