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Transcriptomic analysis of bone and fibrous tissue morphogenesis during digit tip regeneration in the adult mouse
Author(s) -
Qu Feini,
Palte Ilan C.,
Gontarz Paul M.,
Zhang Bo,
Guilak Farshid
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000330r
Subject(s) - blastema , regeneration (biology) , numerical digit , hox gene , morphogenesis , biology , microbiology and biotechnology , transcriptome , anatomy , stem cell , progenitor cell , limb development , wound healing , regenerative medicine , pathology , gene expression , gene , immunology , medicine , genetics , embryo , arithmetic , mathematics
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.