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

Int J Cardiol. 2016 Apr 15:209:296-306. doi: 10.1016/j.ijcard.2016.02.040. Epub 2016 Feb 4.

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.

Methods and 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.

Keywords: Adult stem cells; Atrial appendage; Cell transdifferentiation; Heart; Macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atrial Appendage / cytology
  • Atrial Appendage / physiology*
  • Cells, Cultured
  • Cellular Reprogramming Techniques / methods
  • Hematopoietic Stem Cells / physiology*
  • Leukocyte Common Antigens / physiology*
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype*
  • Proto-Oncogene Proteins c-kit / physiology*

Substances

  • Proto-Oncogene Proteins c-kit
  • Leukocyte Common Antigens
  • Ptprc protein, mouse