Single-Cell Transcriptomics Reveals Early Effects of Ionizing Radiation on Bone Marrow Mononuclear Cells in Mice

Area of Science:

• Hematology
• Radiation Biology
• Immunology

Background:

• The hematopoietic system is highly sensitive to ionizing radiation.
• Bone marrow cell population heterogeneity complicates understanding radiosensitivity.
• Limited data exists on radiosensitivity across diverse hematopoietic cell types.

Purpose of the Study:

• To investigate the radiosensitivity of different bone marrow hematopoietic cell populations.
• To identify molecular mechanisms underlying differential radiosensitivity.
• To explore early gene expression responses to radiation in these cells.

Main Methods:

• Irradiation of bone marrow cells.
• Cell counting to assess population changes.
• Single-cell transcriptome sequencing to analyze gene expression profiles.

Main Results:

• Granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells, and B cells were most radiosensitive.
• Neutrophils, NK cells, T cells, and dendritic cells exhibited radioresistance, with neutrophils being most resistant.
• Distinct gene expression profiles were observed between radiosensitive and radioresistant cells.
• B cells showed upregulation of mitochondrial respiratory chain genes post-irradiation.
• Neutrophils displayed fewer gene alterations, suggesting unique resistance mechanisms.

Conclusions:

• Hematopoietic cell radiosensitivity is heterogeneous.
• Mitochondrial function may link to B cell radiosensitivity.
• Neutrophils possess distinct radioresistance mechanisms.
• This study elucidates molecular insights into bone marrow cell radiosensitivity diversity.