Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma

Area of Science:

• Immunology
• Genomics
• Cell Biology

Background:

• Understanding immune cell adaptation over time is crucial for biology.
• Existing in vivo genomic technologies lack the ability to capture dynamic cellular changes.

Purpose of the Study:

• To introduce Zman-seq, a novel single-cell technology for recording transcriptomic dynamics in vivo.
• To investigate immune cell-state transitions within the glioblastoma microenvironment.

Main Methods:

• Zman-seq: a single-cell technology that introduces time stamps into circulating immune cells for tracking over days.
• Application of Zman-seq to analyze immune cell trajectories in glioblastoma.

Main Results:

• Cytotoxic natural killer cells transitioned to a dysfunctional state within 24 hours, regulated by TGFB1 signaling.
• Infiltrating monocytes differentiated into immunosuppressive macrophages (upregulating Trem2, Il18bp, Arg1) over 36-48 hours.
• Anti-TREM2 antibody treatment shifted monocyte trajectories towards pro-inflammatory macrophages, altering the tumor microenvironment.

Conclusions:

• Zman-seq enables empirical measurement of cell differentiation trajectories in vivo.
• This technology can advance the development of more effective immunotherapies by revealing dynamic immune responses.