@article{16907e32aeed4d8184418a72558d5e27,
title = "Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse",
abstract = "Humans have limited regenerative potential of musculoskeletal tissues following limb or digit loss. The murine digit has been used to study mammalian regeneration, where stem/progenitor cells (the “blastema”) completely regenerate the digit tip after distal, but not proximal, amputation. However, the molecular mechanisms responsible for this response remain to be determined. Here, we evaluated the spatiotemporal formation of bone and fibrous tissues after level-dependent amputation of the murine terminal phalanx and quantified the transcriptome of the repair tissue. Distal (regenerative) and proximal (non-regenerative) amputations showed significant differences in temporal gene expression and tissue regrowth over time. Genes that direct skeletal system development and limb morphogenesis are transiently upregulated during blastema formation and differentiation, including distal Hox genes. Overall, our results suggest that digit tip regeneration is controlled by a gene regulatory network that recapitulates aspects of limb development, and that failure to activate this developmental program results in fibrotic wound healing.",
keywords = "RNA-seq, amputation, blastema, osteogenesis, regenerative medicine, wound repair",
author = "Feini Qu and Palte, {Ilan C.} and Gontarz, {Paul M.} and Bo Zhang and Farshid Guilak",
note = "Funding Information: This work was supported by the National Institutes of Health (T32 AR060719 and F32 AR074895 to F. Qu, R25 DA027995 to B. Zhang, AG15768 and AG46927 to F. Guilak, P30 AR073752, P30 AR074992), the Arthritis Foundation, the Nancy Taylor Foundation for Chronic Diseases, and the Shriners Hospitals for Children Hoxa13/Hoxd13 Funding Information: This work was supported by the National Institutes of Health (T32 AR060719 and F32 AR074895 to F. Qu, R25 DA027995 to B. Zhang, AG15768 and AG46927 to F. Guilak, P30 AR073752, P30 AR074992), the Arthritis Foundation, the Nancy Taylor Foundation for Chronic Diseases, and the Shriners Hospitals for Children The authors gratefully acknowledge Mr. Nicholas Benshoff for his technical assistance with surgery, Dr. Christopher Rowland and Mrs. Sara Oswald for their imaging expertise, and the Genome Technology Access Center at Washington University in St. Louis for RNA library preparation and sequencing. Publisher Copyright: {\textcopyright} 2020 Federation of American Societies for Experimental Biology",
year = "2020",
month = jul,
day = "1",
doi = "10.1096/fj.202000330R",
language = "English",
volume = "34",
pages = "9740--9754",
journal = "FASEB Journal",
issn = "0892-6638",
number = "7",
}