Cardiac macrophages (cM

) are critical for early postnatal heart regeneration and fibrotic
repair in the adult heart, but their origins and cellular dynamics during postnatal develop
-
ment 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
+
cM

diversifies into
MHCII
+
and MHCII

cells. Genetic fate mapping demonstrated that cM

derived from
CX3CR1
+
embryonic progenitors persisted into adulthood but the initially high contribution
to resident cM

declined after birth. Consistent with this, the early significant prolifera
-
tion rate of resident cM

decreased with age upon diversification into subpopulations.
Bone marrow (BM) reconstitution experiments showed monocyte-dependent quantitative
replacement of all cM

populations. Furthermore, parabiotic mice and BM chimeras of
nonirradiated recipient mice revealed a slow but significant donor contribution to cM

.
Together, our observations indicate that in the heart, embryo-derived cM

show declining
self-renewal with age and are progressively substituted by monocyte-derived macrophages,
even in the absence of inflammation.