The origins of rare glycosylphosphatidylinositol-deficient cells in normal and immune-mediated hematopoiesis.

Rare glycosylphosphatidylinositol-deficient cells in healthy individuals are polyclonal and include long-lived clones, while in acquired aplastic anemia, they expand across lineages.

• Why it matters: Understanding the origins and behavior of these cells can reveal insights into normal hematopoiesis and immune dysregulation, potentially informing treatments for blood disorders.
• What they did: Using single-cell-resolution PIGA sequencing, the study analyzed the clonal composition of GPI-deficient cells in healthy people and patients with acquired aplastic anemia, identifying their lineage expansion patterns.
• The result: Findings show healthy GPI-deficient cells are diverse and long-lasting, whereas in aplastic anemia, PIGA-mutant stem/progenitor cells selectively expand across multiple blood cell lineages, highlighting disease-specific clonal dynamics.