title: Evolution of the c-kit-positive cell response to pathological challenge in the myocardium.
abstract: Cumulative evidence indicates that myocardium responds to growth or injury by recruitment of stem and/or progenitor cells that participate in repair and regenerative processes. Unequivocal identification of this population has been hampered by lack of reagents or markers specific to the recruited population, leading to controversies regarding the nature of these cells. Use of a transgenic mouse expressing green fluorescent protein driven by the c-kit promoter allows for unambiguous identification of this cell population. Green fluorescent protein (GFP) driven by the c-kit promoter labels a fraction of the c-kit+ cells recognized by antibody labeling for c-kit protein. Expression of GFP by the c-kit promoter and accumulation of GFP-positive cells in the myocardium is relatively high at birth compared with adult and declines between postnatal weeks 1 and 2, which tracks in parallel with expression of c-kit protein and c-kit-positive cells. Acute cardiomyopathic injury by infarction prompts increased expression of both GFP protein and GFP-labeled cells in the region of infarction relative to remote myocardium. Similar increases were observed for c-kit protein and cells with a slightly earlier onset and decline relative to the GFP signal. Cells coexpressing GFP, c-kit, and cardiogenic markers were apparent at 1-2 weeks postinfarction. Cardiac-resident c-kit+ cell cultures derived from the transgenic line express GFP that is diminished in parallel with c-kit by induction of differentiation. The use of genetically engineered mice validates and extends the concept of c-kit+ cells participating in the response to myocardial injury.
authors.affiliation: Department of Biology, San Diego State University Heart Institute, San Diego State University, San Diego, California 92182, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Fransioli
authors.forename: Brandi
authors.initials: B
authors.lastname: Bailey
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Gude
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Cottage
authors.forename: John A
authors.initials: JA
authors.lastname: Muraski
authors.forename: Gregory
authors.initials: G
authors.lastname: Emmanuel
authors.forename: Weitao
authors.initials: W
authors.lastname: Wu
authors.forename: Roberto
authors.initials: R
authors.lastname: Alvarez
authors.forename: Marta
authors.initials: M
authors.lastname: Rubio
authors.forename: Sergio
authors.initials: S
authors.lastname: Ottolenghi
authors.forename: Erik
authors.initials: E
authors.lastname: Schaefer
authors.forename: Mark A
authors.initials: MA
authors.lastname: Sussman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D042783:Endothelial Cells / Q000166:cytology; D050991:GATA4 Transcription Factor / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D021381:Protein Transport; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050991:GATA4 Transcription Factor; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit