|
Status |
Public on Apr 28, 2023 |
Title |
An ERK-dependent molecular switch antagonizes fibrosis and promotes regeneration in spiny mice (Acomys) |
Organisms |
Acomys cahirinus; Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
|
Summary |
Although most mammals heal injured tissues and organs with scarring, spiny mice (Acomys) naturally regenerate skin and complex musculoskeletal tissues. Currently, the core signaling pathways driving mammalian tissue regeneration are poorly characterized. Here, we show that, while immediate ERK activation is a shared feature of scarring (Mus) and regenerating (Acomys) injuries, ERK activity is only sustained during complex tissue regeneration. Following ERK inhibition, regeneration in Acomys shifted towards a fibrotic repair. Using scRNA-seq, we uncovered that MAPK/ERK signaling acts in a cell type specific manner to direct regenerative healing. Loss- and gain-of-function experiments prompted us to identify FGF and ErbB signaling as upstream ERK regulators of regeneration. By ectopically activating ERK in Mus injuries, a pro- regenerative response was induced, including cell proliferation, extracellular matrix remodeling and hair follicle neogenesis. Our data provide new insights into why some mammals regenerate better than others and open avenues to redirect fibrotic repair towards regenerative healing.
|
|
|
Overall design |
pERK, FGFR and ErbB2 inhibitors were injected from D12 to D15, similarly to DMSO control; micro-beads soaked with either PBS, recombinant FGF-2/NRG-1 were implanted locally at D10.
|
|
|
Contributor(s) |
Tomasso A, Koopmans T, Lijnzaad P, Bartscherer K, Seifert AW |
Citation(s) |
37126559 |
|
Submission date |
Feb 03, 2023 |
Last update date |
May 12, 2023 |
Contact name |
PHILIP LIJNZAAD |
E-mail(s) |
p.lijnzaad@prinsesmaximacentrum.nl
|
Organization name |
Princess Maxima Center for Pediatric Oncology
|
Department |
Single Cell Facility
|
Lab |
Holstege Lab
|
Street address |
HEIDELBERGLAAN 25
|
City |
UTRECHT |
State/province |
Utrecht |
ZIP/Postal code |
3584 CS |
Country |
Netherlands |
|
|
Platforms (2) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
GPL29848 |
Illumina NovaSeq 6000 (Acomys cahirinus) |
|
Samples (6)
|
|
Relations |
BioProject |
PRJNA931237 |