Definitive Hematopoietic Hierarchy — Multipotent stem cell commitment, megakaryocyte-biased emergency hematopoiesis, and dual-origin tissue macrophage ontogeny.
Hematopoiesis is the continuous physiological process by which the body produces mature cellular blood elements from self-renewing, multipotent Hematopoietic Stem Cells (HSCs) residing in specialized bone marrow niches. Through asymmetric cell division, an HSC generates both a replica to sustain the stem cell pool and a committed progenitor. Differentiation bifurcates into two classical primary branches: the Common Myeloid Progenitor (CMP) lineage (producing erythrocytes, megakaryocytes/platelets, granulocytes, and monocytes) and the Common Lymphoid Progenitor (CLP) lineage (producing B cells, T cells, and NK cells).
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The tree above shows adult, bone-marrow (definitive) hematopoiesis. But many tissue-resident macrophages are not continuously replenished from bone-marrow monocytes — they're seeded during development (yolk sac → fetal liver) and then self-renew locally for years to decades.
Seeded from primitive yolk-sac macrophages before the blood-brain barrier closes (~E8.5-9.5 in mouse). Lifelong local self-renewal; excluded from circulating monocyte input by the intact BBB.
Distinct from parenchymal microglia — sit at CNS borders. Predominantly embryonic-derived and self-renewing, though choroid plexus macrophages show more ongoing monocyte turnover than the meningeal/perivascular subsets.
Seeded via the EMP/fetal-liver wave prenatally. Self-renewing in steady state; monocytes are recruited and can differentiate into Kupffer-like cells mainly after significant liver injury or depletion.
Established from fetal-liver monocytes around birth, then self-renew locally. GM-CSF (via PPAR-gamma) is essential for postnatal maturation and maintenance.
Despite the name and dendritic morphology, these are ontogenetically macrophage-like: an early yolk-sac wave is largely replaced by fetal-liver monocyte-derived cells shortly after birth, which then self-renew locally in adult skin. Minimal bone-marrow input in steady state.
EMP/fetal-liver derived, locally self-renewing; recycle senescent red blood cells and recover iron.
Embryonic-derived, self-renewing, GATA6-dependent transcriptional program. Population share declines with age/inflammation as monocyte-derived cells take over.
Continuously recruited from circulating monocytes, especially during inflammation — the recruited counterpart to the large peritoneal macrophage pool.
A mixed population: an embryonic-derived resident pool is present at baseline but is progressively replaced by monocyte-derived cells with age, and monocyte-derived cells dominate after myocardial infarction.
Continuously replenished from circulating monocytes (the "monocyte waterfall" model) — essentially no stable embryonic-derived population persists into adulthood, unlike most other tissue macrophages.
Distinct from epidermal Langerhans cells — a mixed-origin population with substantial and age-increasing monocyte contribution.
Form a self-renewing, gap-junction-connected (connexin-43) surveillance network, but with meaningful and heterogeneous ongoing monocyte contribution depending on the nephron segment studied.
A modest resident population exists in lean adipose tissue, but the pool expands dramatically from monocyte recruitment in obesity ("metaflammation"), driving insulin resistance.
Multinucleated cells formed by fusion of monocyte/macrophage-lineage precursors. Both embryonic (EMP-derived) precursors seeding developing bone AND adult bone-marrow monocyte-lineage precursors contribute throughout life — a genuinely dual-source population, unlike most entries on this list.
Entities that don't fit cleanly into the branching tree — either because they're the frankly malignant counterpart of a cell already shown, because they break the tidy one-lineage-per-cell premise, or because the name is a trap and the cell isn't even hematopoietic.