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Series GSE224433 Query DataSets for GSE224433
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)
GSM7022154 acomys PD
GSM7022155 acomys TAK
GSM7022156 acomys AZD
Relations
BioProject PRJNA931237

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE224433_RAW.tar 102.9 Mb (http)(custom) TAR (of H5)
GSE224433_cell-metadata.txt.gz 1.3 Mb (ftp)(http) TXT
GSE224433_count_table.txt.gz 67.9 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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