CD66b^-CD64^dimCD115^- cells in the human bone marrow represent neutrophil-committed progenitors

Area of Science:

• Hematopoiesis
• Immunology
• Cell Biology

Background:

• Neutrophils are critical immune cells with complex development pathways.
• Early neutrophil progenitor identification is essential for understanding hematopoiesis and immune disorders.

Purpose of the Study:

• To identify and characterize novel, early-stage human neutrophil progenitor cells.
• To elucidate the differentiation routes and maturation potential of these newly identified progenitors.

Main Methods:

• Flow cytometry and cell sorting to isolate specific bone marrow cell populations.
• In vitro differentiation assays and in vivo adoptive transfer experiments.
• Single-cell RNA-sequencing to analyze transcriptomic profiles and identify differentiation clusters.

Main Results:

• Identification of CD66b-CD64dimCD115- neutrophil-committed progenitor cells (NCPs) in specific bone marrow subsets.
• NCPs exclusively differentiate into CD66b+ neutrophils in vitro and in vivo.
• Single-cell RNA-sequencing revealed four distinct NCP clusters representing different maturation stages and differentiation routes, including one with an interferon-stimulated gene signature.
• NCPs were phenotypically and transcriptomically earlier than previously described neutrophil progenitors.

Conclusions:

• The study identified novel human neutrophil-committed progenitor cells (NCPs), advancing our understanding of early neutrophil ontogeny.
• NCPs represent a crucial early stage in neutrophil development, distinct from previously known progenitors.
• Findings provide a foundation for further research into neutrophil biology and related diseases.