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Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells

Jianpeng Sheng1, Christiane Ruedl1, Klaus Karjalainen1

  • 1School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.

Immunity
|August 20, 2015
PubMed

Insights

Most adult macrophages originate from hematopoietic stem cells (HSCs). Exceptions include microglia and some epidermal Langerhans cells, which derive from the yolk sac (YS). This study clarifies macrophage origins using novel fate mapping.

Area of Science:

  • Immunology
  • Developmental Biology
  • Cell Biology

Background:

  • Macrophages exhibit diverse functions and locations in tissues during health and disease.
  • The precise origins of tissue-resident macrophages, whether from fetal or adult sources, remain a key question in immunology.

Purpose of the Study:

  • To investigate the developmental origins of various adult macrophage populations.
  • To differentiate between embryonic and adult hematopoietic stem cell contributions to tissue macrophages.

Main Methods:

  • Development of a novel Kit locus-based fate mapping mouse model.
  • Induction of precursor labeling at distinct fetal and adult time points.
  • Tracing macrophage populations in various adult tissues to their source.

Main Results:

  • All investigated adult macrophages, both resident and infiltrating, originate from classical hematopoietic stem cells (HSCs).
  • Microglia were confirmed as exclusively yolk sac (YS)-derived.
  • Epidermal Langerhans cells were found to be partially derived from the yolk sac (YS).

Conclusions:

  • Hematopoietic stem cells (HSCs) are the primary source for most adult tissue macrophages.
  • Yolk sac (YS) progenitors contribute to specific macrophage lineages, notably microglia and partially epidermal Langerhans cells.
  • This study provides definitive insights into macrophage ontogeny, crucial for understanding tissue homeostasis and disease pathogenesis.

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