Visualizing the chronicle of multiple cell fates using a near-IR dual-RNA/DNA-targeting probe

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2025

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Sutrisno, L.
Richards, G.J.
Evans, J.D.
Matsumoto, M.
Li, X.
Uto, K.
Hill, J.P.
Taki, M.
Yamaguchi, S.
Ariga, K.

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Science Advances, 2025; 11(43):eadz6633-1-eadz6633-13

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Linawati Sutrisno, Gary J. Richards, Jack D. Evans, Michio Matsumoto, Xianglan Li, Koichiro Uto, Jonathan P. Hill, Masayasu Taki, Shigehiro Yamaguchi, Katsuhiko Ariga

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Abstract

Early detection and late-stage cell fate assessment are key factors to develop therapeutic strategies, although current methods cannot capture early responses or distinguish multiple injury states, especially in ultraviolet-visible (UV-vis)–sensitive cells. Here, we introduce a method to simultaneously detect variations in RNA and DNA under near-infrared photoexcitation. Using a pyrazinacene-based probe (TEG₈-N14), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA/DNA changes. Specifically, TEG₈-N14 selectively stains necrotic cells in live samples, while after fixation, it allows detection of ultraearly senescence in UV-vis–sensitive cells, providing approximately twofold greater informational content than existing RNA or DNA fluorophores. These findings break current imaging barriers by enabling comprehensive visualization of single-cell fate histories without being affected by UV-vis or genetic manipulation.

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© 2025 the Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. no claim to original U.S. Government Works. Distributed under a creative commons Attribution license 4.0 (cc BY).

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