Type 1 interferon perturbates clonal competition by reshaping human blood development.

Interferon-α reshapes human blood development by inducing distinct HSC states, with 50% of mutated stem cells resisting inflammatory myeloid differentiation.

• Why it matters: Understanding how inflammation influences hematopoietic stem cell evolution is crucial for developing therapies for clonal hematopoiesis and myeloid neoplasms, which often involve mutated stem cells that resist treatment.
• What they did: The study used single-cell multiomics to analyze blood cells from patients before and after interferon-α treatment, distinguishing effects on mutated versus wild-type HSCs and their differentiation pathways.
• The result: Interferon-α activated HSCs into lymphoid and myeloid states, normalizing blood counts, but mutated stem cells, especially with CALR or JAK2 mutations, resisted inflammatory myeloid differentiation, impacting clonal fitness.