title: Macrophage precursor cells from the left atrial appendage of the heart spontaneously reprogram into a C-kit+/CD45- stem cell-like phenotype.
abstract: BACKGROUND
  The developmental origin of the c-kit expressing progenitor cell pool in the adult heart has remained elusive. Recently, it has been discovered that the injured heart is enriched with c-kit(+) cells, which also express the hematopoietic marker CD45.
  
  
  RESULTS
  In this study, we characterize the phenotype and transcriptome of the c-kit+/CD45+/CD11b+/Flk-1+/Sca-1±(B-type) cell population, originating from the left atrial appendage. These cells are defined as cardiac macrophage progenitors. We also demonstrate that the CD45+ progenitor cell population activates heart development, neural crest and pluripotency-associated pathways in vitro, in conjunction with CD45 down-regulation, and acquire a c-kit+/CD45-/CD11b-/Flk-1-/Sca-1+ (A-type) phenotype through cell fusion and asymmetric division. This putative spontaneous reprogramming evolves into a highly proliferative, partially myogenic phenotype (C-type).
  
  
  CONCLUSIONS
  Our data suggests that A-type cells and cardiac macrophage precursor cells (B-type) have a common lineage origin, possibly resolving some current conundrums in the field of cardiac regeneration.
authors.affiliation: Cardiovascular Research Centre, Heart Institute, Hadassah-Hebrew University Medical Centre, 91120 Jerusalem, Israel.
authors.forename: Jussi V
authors.initials: JV
authors.lastname: Leinonen
authors.affiliation: Cardiovascular Research Centre, Heart Institute, Hadassah-Hebrew University Medical Centre, 91120 Jerusalem, Israel.
authors.forename: Avishag
authors.initials: A
authors.lastname: Korkus-Emanuelov
authors.affiliation: Department of Immunology, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Yochai
authors.initials: Y
authors.lastname: Wolf
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Milgrom-Hoffman
authors.affiliation: Faculty of Medicine, Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Lichtstein
authors.affiliation: Cardiovascular Research Centre, Heart Institute, Hadassah-Hebrew University Medical Centre, 91120 Jerusalem, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Hoss
authors.affiliation: Cardiovascular Research Centre, Heart Institute, Hadassah-Hebrew University Medical Centre, 91120 Jerusalem, Israel.
authors.forename: Chaim
authors.initials: C
authors.lastname: Lotan
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Eldad
authors.initials: E
authors.lastname: Tzahor
authors.affiliation: Department of Immunology, Weizmann Institute of Science, 7610001 Rehovot, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Cardiovascular Research Centre, Heart Institute, Hadassah-Hebrew University Medical Centre, 91120 Jerusalem, Israel. Electronic address: rbeeri@hadassah.org.il.
authors.forename: Ronen
authors.initials: R
authors.lastname: Beeri
mesh_terms: D000818:Animals; D020517:Atrial Appendage / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D000067470:Cellular Reprogramming Techniques / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology*
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse
keywords: Adult stem cells; Atrial appendage; Cell transdifferentiation; Heart; Macrophages