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VIB researchers have developed a new human stem-cell-based model that recreates an early stage of immune-cell development and shows how a single progenitor population can give rise to specialized macrophages across different organs. The model provides a platform to study how these processes change in disease, and how they might eventually be harnessed therapeutically.

Tissue-resident macrophages are long-lived immune cells that help maintain the health of individual organs. In the brain, they include microglia and border-associated macrophages. Other organs, such as the liver, heart and kidney, have their own specialized macrophage populations.

These cells arise very early in development. Some of their earliest precursors are formed in the yolk sac, a temporary structure that supports the embryo before organs are fully developed. Tracing the origins of these cells in humans has been difficult, as access to embryonic tissue is extremely limited.

In a new study published in Developmental Cell, a research team led by professor Renzo Mancuso (VIB-UAntwerp Center for Molecular Neurology) and professor Bart De Strooper (VIB-KU Leuven Center for Neuroscience & UK DRI) circumvented this issue by recreating this early developmental stage in the lab using human pluripotent stem cells.

From these cells, they generated a population called inducible yolk sac myeloid progenitors, or iYSMPs. Molecular profiling showed that these cells closely resemble progenitors found during early human development.

The team then tested whether these progenitors could reproduce the developmental potential of their embryonic counterparts.

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