Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE131078 | GEO | 2020/06/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression analysis of nail matrix in mouse.

Project description:Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, Î²-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees. Nail matrix cells were harvested from proximal and distal matrix region by microdissection and processed to RNA extraction and hybridization on Affymetrix microarrays. We analyzed two proximal and two distal matrix cells.

2013-03-27 | E-GEOD-45494 | biostudies-arrayexpress

Expression analysis of nail matrix in mouse.

Project description:Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees.

2013-03-27 | GSE45494 | GEO

Three Distinct Phases of Regeneration-Specific Gene Expression in the Axolotl Blastema

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

Spatial transcriptomics reveals increased energetic requirements underpinning age-dependent declines in digit regeneration rescued through administration of OAA

Project description: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.

2022-06-01 | GSE180682 | GEO

Positional information modulates transient regeneration-activated cell states during vertebrate appendage regeneration.

Project description:Injury is a common occurrence in the life of most if not all organisms. Because injury and the extent of damage inflicted are not predictable events, pre-existing tissues must somehow determine how much tissue needs to be restored. It has been known for over a century that amputation position along a proximal-distal (P/D) axis determines the regeneration speed of amputated limbs in regeneration-competent animals1. Yet, it is not clear how an injured limb conveys positional information during regeneration to faithfully restore pre-existing morphologies and functions. Here, we profiled millimetric caudal fins regenerating proximal and distal amputations in the African killifish (Nothobranchius furzeri). We report position-specific, differential modulation of the spatial distribution, duration, and magnitude of proliferation, and the possibility to predict blastema sizes. Regenerating fins profiled by single cell RNA sequencing identified a Transient Regeneration-Activated Cell State (TRACS) enriched in extracellular matrix (ECM) components and modifiers that is proportionally amplified to match a given amputation position. We located this transient cell state to the basal epidermis by gene expression and confocal microscopy, and propose a role for these cells in transducing positional information to the regeneration blastema. Understanding the temporal deployment of regenerative cell states may hold the key to set up a successful regeneration event in organisms with limited regenerative abilities such as humans.

2024-04-01 | GSE260629 | GEO

Single cell RNA sequencing of adult regenerating mouse digit tips

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 single cell RNA sequencing of over 38,000 cells from mouse digit tip blastemas and unamputated control digit tips and generate an atlas of the cell types participating in digit tip regeneration.

2020-02-24 | GSE143888 | GEO

Tig1 regulates proximo-distal identity during salamander limb regeneration

Project description:Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed ‘positional identity’. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/RARRES1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting HoxA13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.

2022-01-30 | GSE184948 | GEO

Sequencing of iMDK-treated regenerating limbs

Project description:Treatment with midkine inhibitor iMDK inhibits limb regeneration. To elucidate the transcriptional mechanisms of iMDK treatment, we sequenced regenerating limbs treated with either DMSO or iMDK (bulk) in biological triplicate at 11 days post-amputation (dpa).

2020-01-15 | GSE132325 | GEO

Transcription profiling time series of Danio rerio heart regeneration

Project description:Amputation of heart tissue followed by regeneration of the heart. Samples were taken at 0 hpa (hours post-amputation), 6 hpa, 12 hpa, 24 hpa, 3 dpa and 5 dpa.

2008-09-05 | E-MEXP-1239 | biostudies-arrayexpress

Gene Expression During the First 28 Days of Axolotl Limb Regeneration

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

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data