In summary: NeuMap redefines how we see neutrophils, not as random variants, but as a structured compartment with defined hubs, trajectories, and conserved principles across biology. This opens new paths for neutrophil-based diagnostics and therapies. 🚀

Perhaps most exciting is its potential in diagnostics. By projecting blood neutrophils from 18 different conditions, we created a “barcode” of disease states. This means circulating neutrophils could reveal the host’s pathophysiological state. 🩸✅

Importantly, NeuMap’s architecture is conserved across sex, genetic background, environmental conditions, AND in humans. We mapped human neutrophil data from healthy, cancer, and lupus samples across 10 different tissues onto NeuMap and identified conserved hubs. 🌍👥

Using multi-omics (DOGMA-seq), we found that key transcription factors like JUNB control angiogenic and immunosuppressive states. Neutrophil-specific deletion of Junb impaired tissue revascularization and blunted tumor growth—validating NeuMap’s predictive power. 🧪

These hubs aren’t isolated—they’re connected by maturation and activation trajectories that shift during health, cancer, or inflammation. RNA velocity and timestamp experiments revealed that neutrophils follow preferred paths depending on the physiological context. 🔁

We discovered neutrophils organize into a finite set of 7 transcriptional “hubs,” each linked to specific functions:
· PreNeu & Immature hubs
· Immune-silent hub (circulating, quiescent)
· IFN-response hub (antiviral)
· Two immunosuppressive/angiogenic hubs
· Ag-presenting hub

NeuMap was constructed using scRNA-seq of ~130,000 neutrophils from bone marrow, blood, lung, liver, gut, tumors, infections, and more—spanning health, inflammation, cancer, and development. This isn’t just another dataset—it’s an integrative map of neutrophil states. 🧭