Macrophage precursor cells from the left atrial appendage of the heart spontaneously reprogram into a C-kit+/CD45− stem cell-like phenotype Academic Article uri icon

abstract

  • 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.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).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

  • Leinonen, Jussi V
  • Korkus-Emanuelov, Avishag
  • Wolf, Yochai
  • Milgrom Hoffman, Michal
  • Lichtstein, David
  • Hoss, Sara
  • Lotan, Chaim
  • Tzahor, Eldad
  • Jung, Steffen
  • Beeri, Ronen

publication date

  • 2016