Calcineurin Controls Proximodistal Blastema Polarity in Zebrafish Fin Regeneration
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ABSTRACT:
PROVIDER: PRJNA669701 | ENA |
REPOSITORIES: ENA
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Project description:Planarian flatworms regenerate their heads and tails from anterior or posterior wounds and this blastema regeneration polarity is controlled by Wnt/β-catenin signaling. It is well known that a regeneration blastema of appendages of vertebrates such as fish and amphibians grows distally. However, it remains unclear whether a regeneration blastema in vertebrate appendages can grow proximally. Here, we show that a regeneration blastema in zebrafish fins can grow proximally along the proximodistal axis by calcineurin inhibition. We used fin excavation in adult zebrafish to observe the unidirectional regeneration, from the anterior cut edge (ACE) to the posterior cut edge (PCE) of the cavity and this unidirectional regeneration polarity occurs as the PCE fails to build blastemas. Furthermore, we found that calcineurin activities in the ACE were greater than in the PCE. Calcineurin inhibition induced the PCE blastemas, and calcineurin hyperactivation suppressed fin regeneration. Collectively, these findings identify calcineurin as a molecular switch to specify the PCE blastema of the proximodistal axis and regeneration polarity in zebrafish fin.
2020-10-20 | GSE159560 | GEO
Project description: Not available
| S-EPMC7812827 | biostudies-literature
Project description:Regeneration depends on the ability of mature cells at the injury site to respond to injury, generating tissue-specific progenitors that incorporate the blastema and proliferate to reconstitute the original organ architecture. The metabolic microenvironment has been tightly connected to cell function and identity during development and tumorigenesis. Yet, the link between metabolism and cell identity at the mechanistic level in a regenerative context remains unclear. The adult zebrafish caudal fin, and bone cells specifically, have been crucial for the understanding of mature cell contribution to tissue regeneration. Here, we use this model to explore the relevance of glucose metabolism for the cell fate transitions preceding new osteoblast formation and blastema assembly. We show that injury triggers a shift in the metabolic profile at early stages of regeneration, enhancing glycolysis at the expense of mitochondrial oxidation. This metabolic switch mediates transcriptional changes that make mature osteoblast amenable to be reprogramed into pre-osteoblasts and induces cell cycle re-entry and progression. Manipulation of the metabolic profile led to severe reduction of the pre-osteoblast pool, diminishing their capacity to generate new osteoblasts, and to a complete abrogation of blastema formation. Overall, our data indicate that metabolic alterations have a powerful instructive role in regulating genetic programs that dictate fate decisions and stimulate proliferation, thereby providing a deeper understanding on the mechanisms regulating blastema formation and bone regeneration.
2022-08-11 | GSE194385 | GEO
Project description:Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-β signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impaired tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation. In addition, 4-MU reduced the expression of genes associated with wound epithelium and blastema function. Treatment with the glycogen synthase 3-kinase inhibitors rescued 4-MU-induced defects in cell proliferation and tail regeneration, even though only a subset of wound epithelium and blastema markers was restored. Our findings uncover a role for HA biosynthesis in zebrafish tail regeneration and its epistatic relationships with other regenerative processes.
2017-03-10 | GSE72422 | 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:Previous studies of zebrafish caudal fin regeneration have shown that multiple genetic programs are moduled through regulatory factors. MicroRNAs are short highly conserved non-coding genes that suppress expression of target genes and thereby control multiple genetic programs. Given their important regulatory roles and evolutionary conservation, we hypothesize that microRNAs define a conserved genetic regulatory circuit important for appendage regeneration. We characterized microRNA expression during zebrafish caudal fin regeneration using small RNA sequencing. The stages of caudal fin regeneration were assayed for mRNA expression using mRNA sequencing. Small RNA and mRNA gene expression profiling during 0 and 4 days post amputation.
2016-06-01 | E-GEOD-74415 | biostudies-arrayexpress
Project description:Background/Aims:The ability of regeneration varies widely from invertebrates to vertebrates. Some animals, for example, flatworms, newts, salamanders, and lower vertebrates have the outstanding ability to regenerate all the organs even the whole individual. Unfortunately, the regenerative capacity of humans extremely attenuates along with the biological evolution and this makes it difficult for humans to recover from damaged or missing organs or tissues, and even cause serious loss of function or death. However, the research on regeneration mechanisms is limited and incomplete so far. Here, we investigated the biological mechanisms of zebrafish caudal fin regeneration. Methods:The zebrafish was used as the research object to analyze the differences of mRNA and ncRNA expressed in new tissues at 0d, 3d, and 7d after caudal fin removal, and analyzed the molecular mechanism of caudal fin regeneration from the perspective of the whole transcriptome. Results: We observed that the amputated caudal fin went through a complex genetic change, especially at 3 dpa. This result showed that genes related to response to cell cycle and wounding might play a role in caudal fin regeneration.The up regulated DEGs at 3 dpa (blastema outgrowth stage) were dramatically enriched in 20 Biological Processes (FDR < 0.05), three of which were cell cycle (GO:0007049), mitotic cell cycle (GO:0000278), and cell cycle process (GO:0022402), one was response to wounding (GO:0009611), etc. Conclusion: Taken together, the results revealed that the DEGs were enriched in numerous biological processes, molecular function, cellular component, and signaling pathways, suggesting that the caudal fin regeneration is a highly complicated process of the molecular mechanism.
2022-04-04 | GSE160909 | GEO
Project description:This study investigated the cell composition and lineage relationships of FACS (fluorescence activated cell sorting)-enriched epidermal, bone forming (osteoblast) and (non-osteoblast) blastemal fin regenerate cells by single cell (sc) RNA sequencing. The repetitive cell harvesting in four-week intervals revealed a constant gene regulation over four successive regeneration rounds in the early outgrowth stage. In addition, the sc RNA dataset uncovered a potential lineage relationship between distal blastema cells and osteoblasts during fin regeneration. These findings, together with the identification of novel fin regenerate markers, advance our understanding of complex tissue regeneration in zebrafish.
2023-12-22 | GSE251828 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE37163: Gene expression data from time course of fin regeneration in Danio rerio (part 1) GSE37164: Gene expression data from time course of fin regeneration in Danio rerio (part 2) Refer to individual Series
2012-11-01 | E-GEOD-37165 | biostudies-arrayexpress
Project description:Here, we investigate the origin and nature of blastema cells that regenerate the adult murine digit tip. We show that Pdgfra-expressing mesenchymal cells in uninjured digits establish the regenerative blastema and are essential for regeneration. Single cell profiling shows that the mesenchymal blastema cells are distinct from both uninjured digit and embryonic limb/digit Pdgfra-positive cells. This unique blastema state is environmentally determined; dermal fibroblasts transplanted into the regenerative, but not non-regenerative, digit express blastema markers and contribute to bone regeneration. Moreover, lineage tracing with single cell profiling indicates that endogenous osteoblasts/osteocytes acquire a blastema mesenchymal transcriptional state and contribute to both dermis and bone regeneration. Thus, mammalian digit tip regeneration occurs via a distinct adult mechanism where the regenerative environment promotes acquisition of a unique blastema state that allows cells from tissues like bone to contribute to regeneration of other mesenchymal tissues such as the dermis.
2019-11-15 | GSE135985 | GEO