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| Status |
Public on Jun 01, 2022 |
| Title |
Spatial transcriptomics reveals increased energetic requirements underpinning age-dependent declines in digit regeneration rescued through administration of OAA |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
De novo limb regeneration after amputation is restricted in mammals to the distal digit tip. Central to this regenerative process is the blastema, a heterogeneous population of lineage-restricted, dedifferentiated cells that ultimately orchestrates the regeneration of the amputated bone and surrounding soft tissue. To investigate skeletal regeneration, we made use of spatial transcriptomics to characterize the transcriptional profile specifically within the blastema. Using this technique, we generated a gene signature with high specificity for the blastema in both our spatial data, as well as other previously published single-cell RNA-sequencing transcriptomic studies. To elucidate potential mechanisms distinguishing regenerative from non-regenerative healing, we applied spatial transcriptomics to an aging model. Consistent with other forms of repair, our digit amputation mouse model showed a significant impairment in regeneration in aged mice. Contrasting young and aged mice, spatial analysis revealed a metabolic shift in aged blastema associated with an increased bioenergetic requirement. This enhanced metabolic turnover was associated with increased hypoxia and angiogenic signaling, leading to excessive vascularization and altered regenerated bone architecture in aged mice. Restoration of this metabolic deficiency using the metabolite oxaloacetate enhanced in vivo bone regeneration. Thus, targeting cell metabolism may be a promising strategy to mitigate aging-induced declines in tissue regeneration.
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| Overall design |
Digits from young (age 6 months) and aged (age 18 months) mice were harvested 10 days after amputation of the distal 1/3 of the P3 phalangeal element. For OAA treatment, aged mice were treated with OAA daily starting at day 10 post amputation and sacrificed at day 21.
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| Contributor(s) |
Sammarco MC, Tower RJ |
| Citation(s) |
35616636 |
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| Submission date |
Jul 22, 2021 |
| Last update date |
Jun 02, 2022 |
| Contact name |
Robert J Tower |
| Organization name |
UTSW
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| Street address |
5323 Harry Hines Blvd
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| City |
Dallas |
| ZIP/Postal code |
75390 |
| Country |
USA |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA749116 |
| SRA |
SRP329535 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE180682_Digit_cropping_and_ID.txt.gz |
487 b |
(ftp)(http) |
TXT |
| GSE180682_RAW.tar |
90.6 Mb |
(http)(custom) |
TAR (of CSV, H5, JPG, JSON, PNG, TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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