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. Methods and results In this stud...

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Bibliographic Details
Published in:International journal of cardiology 2016-04, Vol.209, p.296-306
Main Authors: Leinonen, Jussi V, Korkus-Emanuelov, Avishag, Wolf, Yochai, Milgrom-Hoffman, Michal, Lichtstein, David, Hoss, Sara, Lotan, Chaim, Tzahor, Eldad, Jung, Steffen, Beeri, Ronen
Format: Article
Language:English
Subjects:
Adult stem cells
Animals
Atrial appendage
Atrial Appendage - cytology
Atrial Appendage - physiology
Cardiovascular
Cell transdifferentiation
Cells, Cultured
Cellular Reprogramming Techniques - methods
Heart
Hematopoietic Stem Cells - physiology
Leukocyte Common Antigens - physiology
Macrophages
Macrophages - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phenotype
Proto-Oncogene Proteins c-kit - physiology
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Summary: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.
ISSN:0167-5273
1874-1754
DOI:10.1016/j.ijcard.2016.02.040