FGD5 marks a subpopulation of hematopoietic stem and progenitor cells that resist interferon-γ-mediated differentiation

Hematopoietic stem and progenitor cells (HSPCs) are responsible for the production of all immune and blood cells in both steady state and emergency settings. The rates at which HSPCs divide and differentiate vary widely in accordance with both cell intrinsic and cell extrinsic factors. However, the kinetics of these events remain poorly understood. In prior work, we determined that the inflammatory cytokine interferon-γ (IFN-γ) induces HSPC division and differentiation. Here, we report that a subset of hematopoietic stem cells (HSCs) that express Fgd5 do not divide or differentiate in response to IFN-γ. This suggests that FGD5 marks a subset of HSCs that remains unperturbed during emergency hematopoiesis and is potentially a mechanism of preservation of the HSC compartment.