Multiple cell populations generate macrophage progenitors in the early yolk sac

Area of Science:

• Developmental biology
• Hematopoiesis
• Immunology

Background:

• Yolk sac (YS) CSF1 receptor positive (CSF1R+) cells are considered progenitors of tissue-resident macrophages.
• Erythroid-myeloid progenitors (EMPs) in the YS are thought to give rise to these CSF1R+ cells.
• The precise origin of CSF1R+ lineage from diverse early YS hematopoietic progenitors remains unclear.

Purpose of the Study:

• To investigate the timing of CSF1R+ progenitor appearance in the early YS.
• To identify the specific hematopoietic progenitor types that differentiate into CSF1R+ cells.
• To clarify the contribution of EMPs versus other progenitors to the CSF1R+ lineage.

Main Methods:

• Analysis of CSF1R+ cell presence and differentiation potential in the YS at different embryonic days (E8, E9).
• Characterization of hematopoietic progenitors in the early YS.
• Investigation of gene expression dynamics (PU.1 and GATA1) during CSF1R+ lineage emergence.

Main Results:

• CSF1R+ cells appear in the YS by embryonic day 9 (E9).
• The earliest progenitors capable of differentiating into CSF1R+ cells are present in the YS at E8.
• These early progenitors also generate primitive erythroid cells, suggesting shared ancestry.
• By E9, myeloid-restricted and multipotent progenitors in the YS can directly generate CSF1R+ cells.
• Mutual antagonism between PU.1 and GATA1 is observed during CSF1R+ cell emergence.

Conclusions:

• EMPs are not the sole source of the CSF1R+ lineage.
• Multiple hematopoietic progenitor populations in the early YS contribute to the CSF1R+ lineage.
• The origin of tissue-resident macrophages is more complex than previously thought, involving diverse early progenitors.