Deep inside your bones, your body is constantly making millions of red blood cells every second. Scientists at Northwestern Medicine in Illinois just discovered something surprising: the way humans build these essential cells is completely different from what researchers have believed for decades. Their findings, published in the journal Nature Genetics, could change how we understand and treat blood diseases.
For a long time, scientists thought human red blood cells formed in tiny structures called erythroblastic islands, or EBIs, that work like nurseries. The prevailing understanding, based on mouse studies, said these islands always had a central macrophage at their core—a special kind of white blood cell that helps clean up debris.
But using a powerful technology called spatial transcriptomics, which maps gene activity inside whole tissues, researchers found something unexpected. In humans, red blood cells cluster together on their own without needing any central macrophage at all. They stick to each other using a molecule called ICAM4. Mice, meanwhile, still follow the old model, with macrophages marked by a protein called C1q sitting at the center of their clusters.
"The most surprising finding is that the structure of these niches is species-specific," said Dr. Peng Ji, the study's lead researcher and a professor at Northwestern University's Department of Pathology. "In humans, the erythroid cells cluster on their own without needing a central macrophage. That overturns a long-standing assumption that human blood formation mirrors what we see in mice."
Dr. Ji called this a paradigm shift—meaning it changes the basic way scientists think about biology. When the team examined bone marrow from patients with myelodysplastic syndromes, a blood disease that often causes anemia, they found these cell clusters were disrupted. But the damage wasn't permanent: treatment partially restored the clusters, suggesting their structure might influence how patients recover.
The discovery matters because so much medical research relies on mouse experiments. If the underlying biology differs between species, that affects how scientists understand diseases and develop treatments. The findings also open new questions about how human bodies handle cleanup during red blood cell production, since macrophages in mice help remove bits of cells that get expelled during maturation.
Looking ahead, Dr. Ji and his team want to figure out what compensates for the missing macrophage in humans—whether other cells step in to do that cleanup work or if different mechanisms take over. The research points toward a bigger goal: building medical approaches that truly reflect how human bodies actually work.
"Our goal is to move toward models and therapies that truly reflect how human systems work," Ji said. That shift in thinking could eventually lead to better treatments for blood diseases affecting millions of people worldwide.