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Progressive replacement of embryo-derived cardiac macrophages with age
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2014
- Publisher :
- Rockefeller University Press, 2014.
-
Abstract
- Molawi et al. examine the origin and cellular dynamics of macrophages in the heart during postnatal development. Cardiac macrophages derived from CX3CR1+ embryonic progenitors persist into adulthood, but the contribution of these cells to resident macrophages declines after birth with diminished self-renewal as the mice age. Over time, the heart is progressively reconstituted with bone marrow–derived macrophages, even in the absence of inflammation.<br />Cardiac macrophages (cMΦ) are critical for early postnatal heart regeneration and fibrotic repair in the adult heart, but their origins and cellular dynamics during postnatal development have not been well characterized. Tissue macrophages can be derived from embryonic progenitors or from monocytes during inflammation. We report that within the first weeks after birth, the embryo-derived population of resident CX3CR1+ cMΦ diversifies into MHCII+ and MHCII− cells. Genetic fate mapping demonstrated that cMΦ derived from CX3CR1+ embryonic progenitors persisted into adulthood but the initially high contribution to resident cMΦ declined after birth. Consistent with this, the early significant proliferation rate of resident cMΦ decreased with age upon diversification into subpopulations. Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative replacement of all cMΦ populations. Furthermore, parabiotic mice and BM chimeras of nonirradiated recipient mice revealed a slow but significant donor contribution to cMΦ. Together, our observations indicate that in the heart, embryo-derived cMΦ show declining self-renewal with age and are progressively substituted by monocyte-derived macrophages, even in the absence of inflammation.
- Subjects :
- EXPRESSION
HOMEOSTASIS
Immunology
Population
Mice, Transgenic
Inflammation
Research & Experimental Medicine
Biology
DENDRITIC CELLS
Monocytes
Immunophenotyping
Andrology
Mice
INFLAMMATION
REVEALS
medicine
Animals
Immunology and Allergy
Progenitor cell
education
Cell Proliferation
education.field_of_study
Science & Technology
ADULT LIFE
Macrophages
Myocardium
Regeneration (biology)
Age Factors
Brief Definitive Report
PATHWAYS
Cell Differentiation
Embryo
11 Medical And Health Sciences
Embryonic stem cell
TISSUE-RESIDENT MACROPHAGES
SELF-RENEWAL
Phenotype
medicine.anatomical_structure
Medicine, Research & Experimental
Animals, Newborn
Cardiovascular and Metabolic Diseases
Antigens, Surface
Female
Bone marrow
medicine.symptom
Life Sciences & Biomedicine
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 211
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....6697308f4ab706939b8cbe021473d0e9