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Kirschenbaum, D.* ; Xie, K.* ; Ingelfinger, F.* ; Katzenelenbogen, Y.* ; Abadie, K.* ; Look, T.* ; Sheban, F.* ; Phan, T.S.* ; Li, B.* ; Zwicky, P.* ; Yofe, I.* ; David, E.* ; Mazuz, K.* ; Hou, J.* ; Chen, Y.* ; Shaim, H.* ; Shanley, M.* ; Becker, S. ; Qian, J.* ; Colonna, M.* ; Ginhoux, F.* ; Rezvani, K.* ; Theis, F.J. ; Yosef, N.* ; Weiss, T.* ; Weiner, A.* ; Amit, I.*

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

Cell 187, 149-165.e23 (2024)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Deciphering the cell-state transitions underlying immune adaptation across time is fundamental for advancing biology. Empirical in vivo genomic technologies that capture cellular dynamics are currently lacking. We present Zman-seq, a single-cell technology recording transcriptomic dynamics across time by introducing time stamps into circulating immune cells, tracking them in tissues for days. Applying Zman-seq resolved cell-state and molecular trajectories of the dysfunctional immune microenvironment in glioblastoma. Within 24 hours of tumor infiltration, cytotoxic natural killer cells transitioned to a dysfunctional program regulated by TGFB1 signaling. Infiltrating monocytes differentiated into immunosuppressive macrophages, characterized by the upregulation of suppressive myeloid checkpoints Trem2, Il18bp, and Arg1, over 36 to 48 hours. Treatment with an antagonistic anti-TREM2 antibody reshaped the tumor microenvironment by redirecting the monocyte trajectory toward pro-inflammatory macrophages. Zman-seq is a broadly applicable technology, enabling empirical measurements of differentiation trajectories, which can enhance the development of more efficacious immunotherapies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cancer ; Computational Biology ; Dynamics ; Glioblastoma ; Immunology ; Immunotherapy ; Single-cell Biology ; Systems Immunology ; Temporal Transcriptomics ; Tumor-associated-macrophages; Tumor-associated Macrophages; Resistant Acid-phosphatase; Nk Cells; Natural-killer; Growth-factor; Rna-seq; Expression; Regulators; Trem2; Polarization
Sprache englisch
Veröffentlichungsjahr 2024
Prepublished im Jahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Zeitschrift Cell
Quellenangaben Band: 187, Heft: 1, Seiten: 149-165.e23 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge, Mass.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-503800-004
G-503800-001
Förderungen Azrieli Graduate Fellowship - Fulbright Scholarship
EMBO postdoctoral fellowship
postdoctoral fellowship of the Swiss Friends of the Weizmann Institute of Science and of the Azrieli Foundation - Koshland award
DOI 10.1016/j.cell.2023.11.032
WOS ID 001152765900001
Scopus ID 85181724036
PubMed ID 38134933
Erfassungsdatum 2024-01-09
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