Senescent cells promote progenitor cell expansion during axolotl limb regeneration
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ABSTRACT:
PROVIDER: PRJNA849781 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Identifying the genetic program that induces limb regeneration in salamanders is an important resource for regenerative medicine, which currently lacks tools to promote regeneration of functional body structures. The genetic network underlying limb regeneration has been elusive due to the complexity of the injury response that occurs concomitant to blastema formation. Here we performed parallel expression profile time courses of non-regenerative lateral wounds versus amputated limbs in axolotl. We show that limb regeneration occurs in three distinguishable phases--early wound healing followed by a transition phase leading to establishment of the limb development program. By focusing on the transition phase, we identified 93 strictly regeneration-associated genes involved in oxidative stress response, chromatin modification, epithelial development and limb development. The specific expression of the genes was confirmed by in situ hybridization. Regeneration-specific expression databases are critical resources for understanding how regeneration-relevant phenotypes can be induced from adult cells Regeneration of the axolotl forelimb lower arm was compared with the healing of a deep lateral injury in a high density timecourse (uncut, 3h, 6h, 9h, 12h, 24h, 36h, 52h, 72h, 120h, 168h, 288h and 528h after injury). Three independent biological replicates were performed using separate cluches of animals. Amputated and lateral wound samples were made as matched contralateral samples of four pooled animals per timepoint.
2013-01-01 | E-GEOD-36451 | biostudies-arrayexpress
Project description:Discovery of genes driving axolotl limb regeneration has been challenging due to limited genomic resources. We assembled 42 RNA-Seq samples totaling approximately 1.3 billion 100 base paired-end reads using Trinity (Grabherr M.G. et al, Nature Biotechnology, 2011; Haas B.J. et al, Nature Protocols, 2013): https://github.com/trinityrnaseq/trinityrnaseq/wiki). We created a transcriptome with complete sequence information for most axolotl genes, identified transcriptional profiles that distinguish blastemas from differentiated limb tissues, and uncovered functional roles for cirbp and kazald1 in limb regeneration.
2016-12-15 | GSE92429 | GEO
Project description:Axolotl limb regeneration proceeds through the formation of a blastema, a mound of progenitor cells that accumulate at the end of the amputated stump. These progenitor cells expand and later undergo patterning to regenerate the missing limb, restoring both form and function. A subset of cells within the blastema become senescent, a state of permanent growth arrest. Here, we address the functional relevance of cellular senescence to axolotl limb regeneration, through a combination of gain- and loss-of-function assays. Using transcriptomic analyses on in vitro and in vivo senescent cells, we gain insights into the basis of the senescent phenotype, cell-cycle arrest, and molecular mediators involved in axolotl regeneration at the molecular level.
2023-07-10 | GSE206237 | GEO
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. The distal 1.0mm of heterogeneous tissue from regenerating limb tip were removed and used for RNA extraction. 10 samples were collected for each of 20 time points.
2015-04-20 | E-GEOD-67118 | biostudies-arrayexpress
Project description:Axolotl limb regeneration proceeds through the formation of a blastema, a mound of progenitor cells that accumulate at the end of the amputated stump. These progenitor cells expand and later undergo patterning to regenerate the missing limb, restoring both form and function. A subset of cells within the blastema become senescent, a state of permanent growth arrest. Here, we address the functional relevance of cellular senescence to axolotl limb regeneration, through a combination of gain- and loss-of-function assays. Using transcriptomic analyses on in vitro and in vivo senescent cells, we gain insights into the basis of the senescent phenotype, cell-cycle arrest, and molecular mediators involved in axolotl regeneration at the molecular level.
2023-07-10 | GSE206234 | GEO
Project description:Axolotl limb regeneration proceeds through the formation of a blastema, a mound of progenitor cells that accumulate at the end of the amputated stump. These progenitor cells expand and later undergo patterning to regenerate the missing limb, restoring both form and function. A subset of cells within the blastema become senescent, a state of permanent growth arrest. Here, we address the functional relevance of cellular senescence to axolotl limb regeneration, through a combination of gain- and loss-of-function assays. Using transcriptomic analyses on in vitro and in vivo senescent cells, we gain insights into the basis of the senescent phenotype, cell-cycle arrest, and molecular mediators involved in axolotl regeneration at the molecular level.
2023-07-10 | GSE206235 | GEO
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:Identifying the genetic program that induces limb regeneration in salamanders is an important resource for regenerative medicine, which currently lacks tools to promote regeneration of functional body structures. The genetic network underlying limb regeneration has been elusive due to the complexity of the injury response that occurs concomitant to blastema formation. Here we performed parallel expression profile time courses of non-regenerative lateral wounds versus amputated limbs in axolotl. We show that limb regeneration occurs in three distinguishable phases--early wound healing followed by a transition phase leading to establishment of the limb development program. By focusing on the transition phase, we identified 93 strictly regeneration-associated genes involved in oxidative stress response, chromatin modification, epithelial development and limb development. The specific expression of the genes was confirmed by in situ hybridization. Regeneration-specific expression databases are critical resources for understanding how regeneration-relevant phenotypes can be induced from adult cells
2013-01-01 | GSE36451 | 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