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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageAmerican English
Pages (from-to)296-306
Number of pages11
JournalInternational Journal of Cardiology
Volume209
DOIs
StatePublished - 15 Apr 2016

Bibliographical note

Funding Information:
This work was supported by a grant 2005250 , from the US–Israel Binational Science Foundation ( www.BSF.org.il ) and grant R01HL072265 from NIH/NHLBI (to Dr. Beeri) ( www.nhlbi.nih.gov ). Dr. Leinonen was supported by a grant from the Finnish Foundation for Cardiovascular Research , Helsinki, Finland ( www.sydantutkimussaatio.fi ). Program for upgrading the Flow Cytometry laboratory in the Core Research Facility of the Hebrew University of Jerusalem was supported by a grant from USAID's American Schools and Hospitals Abroad (ASHA) ( www.usaid.gov ).

Publisher Copyright:
© 2016 Elsevier Ireland Ltd. All rights reserved.

Keywords

  • Adult stem cells
  • Atrial appendage
  • Cell transdifferentiation
  • Heart
  • Macrophages

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