title: Multi-tissue microarray analysis identifies a molecular signature of regeneration.
abstract: The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt Notophthalmus viridescens. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine.
authors.affiliation: Department of Pediatrics, Northwestern University, Feinberg School of Medicine and Children's Memorial Research Center, Chicago, Illinois, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Mercer
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Cheng
authors.forename: Donald L
authors.initials: DL
authors.lastname: Atkinson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Krcmery
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Guzman
authors.forename: David T
authors.initials: DT
authors.lastname: Kent
authors.forename: Katherine
authors.initials: K
authors.lastname: Zukor
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Marx
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Odelberg
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Simon
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D007109:Immunity; D009673:Notophthalmus viridescens / Q000276:immunology / Q000502:physiology; D009928:Organ Specificity; D012038:Regeneration; D015203:Reproducibility of Results; D015398:Signal Transduction; D046888:Tissue Array Analysis