Adult Bone Marrow Harbors Embryonic-Like Progenitors That Generate Immune Cells Without Monocytes

Adult bone marrow harbors a newly discovered cell type that revives an embryonic pathway to build immune cells, challenging long-held assumptions about how the body repairs itself. The study was published in Nature Immunology (doi.org/10.1038/s41590-026-02686-1) and reveals an alternative route for generating specialized macrophages and other blood lineages independently of circulating monocytes.

Uncovering a Hidden Progenitor in Adult Tissue

For decades, textbook biology has taught that adult tissue-resident macrophages are replenished exclusively by circulating white blood cells known as monocytes during inflammation and cancer. Researchers set out to investigate the exact origins of perivascular macrophages, which are specialized immune cells that line blood vessels and help regulate local inflammation. By tracking genetic reporters in mice, the team noticed that a specific subset of these vessel-lining cells did not originate from standard monocyte pathways.

Instead, advanced single-cell RNA sequencing and flow cytometry pointed toward a rare, distinct population residing inside the bone marrow. The authors named these cells erythro-myeloid progenitors, or EMPROR for short. While traditional hematopoietic stem cells give rise to a broad spectrum of blood cells, EMPROR cells carry a distinct molecular signature that bridges adult physiology with early embryonic development.

Molecular Signatures and Multilineage Potential

Further laboratory assays demonstrated that EMPROR cells possess a restricted yet powerful developmental repertoire. When isolated and tested in culture or transplanted into animal models, these cells successfully generated red blood cells, platelets, neutrophils, and specialized macrophages. They notably lacked the ability to produce dendritic cells or lymphocytes, setting them apart from common monocyte and lymphoid precursors.

Transcriptional profiling showed that adult EMPROR cells share striking similarities with embryonic erythro-myeloid progenitors found during fetal development. They expressed genes typical of early precursors while lacking classic adult monocyte markers such as Csf1r and Ccr2. This absence of standard receptors explains why these cells operate independently of the chemical signaling pathways normally required to recruit conventional monocytes to sites of injury or tumor growth.

Challenging Dogma in Inflammation and Cancer

The discovery reshapes our understanding of how tissues respond to pathological stress, such as solid tumors. When researchers implanted breast cancer cells into experimental mouse models, EMPROR cells actively migrated and generated tumor-associated macrophages and neutrophils. Furthermore, experiments using mice genetically engineered to lack the Ccr2 receptor showed that these specialized vessel-lining macrophages still developed successfully without standard monocyte recruitment.

The findings suggest that the adult body maintains a dormant reservoir of embryonic-like stem cells ready to step in when specific tissues need specialized repair. Because these experiments were conducted in murine models, future investigations will need to determine whether similar progenitor populations exist in humans and what exact roles they play in chronic inflammatory diseases.

The research was published in Nature Immunology on November 1, 2026.