Gene Expression During the First 28 Days of Axolotl Limb Regeneration
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ABSTRACT:
ORGANISM(S): Ambystoma mexicanum
SUBMITTER: Stephen Voss
PROVIDER: E-GEOD-67118 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Here we report the results of a robust microarray experiment that examined the first 28 days of axolotl forelimb regeneration. At each of 20 post-amputation time points, we estimated gene expression for 10 replicate RNA samples that were isolated from 1m of heterogeneous tissue collected from the distal limb tip.
2015-04-20 | GSE67118 | GEO
Project description:The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we have performed deep RNA sequencing of the blastema over a time course. We find genes expressed in three phases with a prominent burst in oncogene expression during the first day, blastemal/limb bud genes peaking at 7 to 14 days, and markers for terminal differentiation upregulated later. We compare these expression patterns to those in a mouse digit amputation model to identify genes specific to the regenerative response. We find that limb patterning genes, SALL genes, and genes involved in the proteasome, adult stem cell, embryonic stem cell, retinoid metabolism, and WNT and NOTCH signaling are regeneration-specific. We establish the “Axolomics” Database, which provides a tool for depositing, retrieving, and searching axolotl-related “omic” information. The experiment includes two time course data sets. One is from mouse digit amputation, another is from Axolotl digit amputation
2013-09-01 | E-GEOD-34394 | biostudies-arrayexpress
Project description:The salamander has the remarkable ability to regenerate its limb after amputation. Cells at the site of amputation form a blastema and then proliferate and differentiate to regrow the limb. To better understand this process, we have performed deep RNA sequencing of the blastema over a time course. We find genes expressed in three phases with a prominent burst in oncogene expression during the first day, blastemal/limb bud genes peaking at 7 to 14 days, and markers for terminal differentiation upregulated later. We compare these expression patterns to those in a mouse digit amputation model to identify genes specific to the regenerative response. We find that limb patterning genes, SALL genes, and genes involved in the proteasome, adult stem cell, embryonic stem cell, retinoid metabolism, and WNT and NOTCH signaling are regeneration-specific. We establish the “Axolomics” Database, which provides a tool for depositing, retrieving, and searching axolotl-related “omic” information.
2013-09-01 | GSE34394 | GEO
Project description:Purpose: Investigate the transcriptomic landscape throughout the time course of murine digit regeneration after level-dependent amputation. Methods: The terminal phalanx bone of hind limb digits was subjected to either a distal amputation (25% bone length loss) or proximal amputation (65% bone length loss). Total RNA was isolated from bone and fibrous tissues distal to the distal interphalangeal joint at 12, 14, and 21 days post-amputation (DPA). mRNA library was sequenced using Illumina HiSeq 3000. Trimmed reads were aligned to the mouse genome mm10 and batch-corrected. Results: A limb-specific developmental signaling pathway is transiently upregulated at 14 DPA after distal amputation, corresponding with regeneration of digit tip tissues. Absence of a limb-specific pathway after proximal amputation corresponded with minimal regeneration and fibrotic scarring. Conclusions: Digit regeneration is a level-dependent and spatiotemporally controlled process, with distal and proximal amputations showing significant differences in gene expression and tissue regrowth over time.
2020-06-10 | GSE131078 | GEO
Project description:Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. Connective tissue (CT) – skeleton, periskeleton, tendon, dermis, interstitial cells – contributes the vast majority of cells that populate the blastema, however it is unclear how individual CT cells may reprogram their fate in order to rebuild the tetrapod limb. Here we use a combination of Cre-loxP reporter lineage tracking and single-cell (sc) RNA-seq to molecularly track, for the first time, adult CT cell heterogeneity and its transition to a limb blastema state. We uncover a multi-phasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that participates in inflammation and extracellular matrix disassembly prior to proliferation, establishment of positional information, and ultimately re-differentiation. While the early regeneration transcriptome states are unique to the blastema, the later stages recapitulate embryonic limb development. Notably, we do not find evidence of a pre-existing blastema-like precursor nor limb bud-like progenitors in the uninjured adult tissue. However, we find that distinct CT subpopulations in the adult limb differentially contribute to proximal and distal portions of the regenerated limb. Together, our data illuminates molecular and cellular reprogramming during complex organ regeneration in a vertebrate.
2018-09-27 | GSE106269 | GEO
Project description:Humans and other tetrapods are considered to require apical-ectodermal-ridge, AER, cells for limb development, and AER-like cells are suggested to be re-formed to initiate limb regeneration. Paradoxically, the presence of AER in the axolotl, the primary regeneration model organism, remains controversial. Here, by leveraging a single-cell transcriptomics-based multi-species atlas, composed of axolotl, human, mouse, chicken, and frog cells, we first established that axolotls contain cells with AER characteristics. Surprisingly, further analyses and spatial transcriptomics revealed that axolotl limbs do not fully re-form AER cells during regeneration. Moreover, the axolotl mesoderm displays part of the AER machinery, revealing a novel program for limb (re)growth. These results clarify the debate about the axolotl AER and the extent to which the limb developmental program is recapitulated during regeneration.
2023-09-20 | GSE243225 | GEO
Project description:Innate regeneration following digit tip amputation is one of the few examples of epimorphic regeneration in mammals. Digit tip regeneration is mediated by the blastema, the same structure invoked during limb regeneration in some lower vertebrates. By genetic lineage analyses in mice, the digit tip blastema has been defined as a population of heterogeneous, lineage restructed progenitor cells. These previous studies, however, do not comprehensively evaluate blastema heterogeneity or address lineage restruction of closely related cell types. Here we report one additional single cell RNA sequencing sample (28 days post-amputation) to add to our already published 38,000 cells from mouse digit tip blastemas and unamputated control digit tips used to generate an atlas of the cell types participating in digit tip regeneration.
2024-07-03 | GSE267446 | GEO
Project description:In this project, we studied the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by means of LC-MS/MS technology. We quantified a total of 714 proteins having an adjusted p < 0.01 with FC greater or equal to 2 between two conditions. Principal component analysis revealed a conspicuous clustering between neotenic and metamorphic samples at 7 days post-amputation. Different set of proteins was identified as differentially expressed at all of the time points (1, 4, and 7 days post-amputations against day0) for neotenic and metamorphic stages. Although functional enrichment analyses underline the presence of common pathways between regenerative and non-regenerative stages, cell proliferation and its regulation associated pathways, immune system related pathways and muscle tissue and ECM remodeling and degradation pathways were represented at different rate between both stages.
2019-11-25 | PXD014806 | Pride
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:The goal of this experiment is to track cellular regeneration after a dorsal injury to the axolotl pallium. To this end, we employed Div-seq, that is, performed snRNA-seq on cells labelled with EdU, which have thus recently replicated. We performed this in a time course, in order to observed the cell populations that were generated as regeneration progressed.
2022-07-20 | E-MTAB-11638 | biostudies-arrayexpress