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| Status |
Public on May 24, 2021 |
| Title |
Fibroblast Dedifferentiation as a Determinant of Successful Regeneration |
| Organisms |
Ambystoma mexicanum; Xenopus laevis |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Limb regeneration, while observed lifelong in salamanders, is restricted to pre-metamorphic stages in Xenopus laevis frogs. After amputation, post-metamorphic frogs form a blastema that grows only an unsegmented cartilage rod. Whether this loss is due to systemic factors such as the immune system or due to an intrinsic incapability of cells to form competent stem cells has been unclear. Here, we use genetic fate mapping to establish that, as in axolotl, connective tissue (CT) cells form the post-metamorphic frog blastema. Using heterochronic transplantation into the limb bud and single-cell transcriptomic profiling, we show that axolotl CT cells fully dedifferentiate and integrate to form lineages including cartilage in the developing limb. In contrast, frog blastema CT cells do not fully re-express the limb bud progenitor program, even when transplanted into the limb bud. Correspondingly, transplanted cells contribute to extraskeletal CT but not to developing cartilage. Further, using single-cell RNA-seq analysis we find that the embryonic and the adult frog cartilage differentiation programs are molecularly distinct. This work defines intrinsic restrictions in CT dedifferentiation as a limitation in adult regeneration.
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| Overall design |
Tissue grafting, single-cell transcriptomics, reporter lineage tracking and cell transplantions were used to deconstruct cell compositions and to reconstruct lineage relationships aiming to find determinants of the successful regeneration in axolotl compared to the incomplete regenration in frogs.
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| Contributor(s) |
Gerber T, Treutlein B |
| Citation(s) |
34004152 |
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| Submission date |
Feb 01, 2021 |
| Last update date |
May 24, 2021 |
| Contact name |
Tobias Gerber |
| E-mail(s) |
tobias.gerber@embl.de
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| Organization name |
EMBL Heidelberg
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| Department |
Developmental Biology
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| Lab |
Detlev Arendt
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| Street address |
Meyerhofstr. 1
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| City |
Heidelberg |
| ZIP/Postal code |
69117 |
| Country |
Germany |
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| Platforms (3) |
| GPL22800 |
Illumina HiSeq 2500 (Ambystoma mexicanum) |
| GPL27159 |
Illumina NovaSeq 6000 (Ambystoma mexicanum) |
| GPL28901 |
Illumina NovaSeq 6000 (Xenopus laevis) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA698552 |
| SRA |
SRP304111 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE165901_RAW.tar |
1.8 Gb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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