Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse
Year: 2020
Type: article
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.
Source: The FASEB Journal
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Arthritis Foundation, Nancy Taylor Foundation for Chronic Diseases, Washington University in St. Louis, Shriners Hospitals for Children, National Institutes of Health, National Institute on Aging, National Institute on Drug Abuse, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1201556103, G1220868724, G2775599718, G3895366428, RESEARCH EDUCATION PROGRAM ON COMPUTATIONAL AND STATISTICAL TOOL DEVELOPMENT FOR ADDICTION GENETICS, G4650882932, G5039167063, G5330480267, G5588909404, G7008996325, G8840517274, G9000004556, G9000059615, G9000095197, G9000108560, G9000110435, G9000217772, G9000308115, Washington University Rheumatic Diseases Research Resource-based Center
OpenAlex ID: W3033577414
