Dynamic Schlafen 11 (SLFN11) expression revealed by single-cell RNA sequencing of clonal human cancer cells
- 1National Institutes of Health National Cancer Institute
Abstract
Schlafen 11 (SLFN11) is a key determinant of sensitivity to DNA-damaging therapies in multiple cancers including leukemia, Ewing sarcoma, head and neck cancers, mesothelioma and small cell lung cancer (SCLC). Here, utilizing immunofluorescence microscopy and single-cell RNA sequencing we characterized SLFN11 expression across eight different human cancer cell lines and found cell-to-cell heterogenous expression both at the protein and RNA levels. Gene set enrichment and pathway analyses show that SLFN11 is coexpressed with a distinct stress-response state and enhanced genome maintenance programs while being inversely correlated with protein translation pathways. Publicly available single-cell RNA-sequencing datasets of human SCLC tumors confirmed the heterogeneous distribution of SLFN11 expression and confirmed its association with replication-related transcriptional programs. These findings indicate that heterogeneous SLFN11 expression reflects dynamic regulation at the single-cell level. They also underscore the limitations of bulk proteomic and transcriptome profiling and point to a potential reservoir of intrinsic chemotherapy resistance.
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BibTeX
@misc{taniyama2026dynamic,
title = {{Dynamic Schlafen 11 (SLFN11) expression revealed by single-cell RNA sequencing of clonal human cancer cells}},
author = {D. Taniyama and Y. Inoue and F. Elloumi and Y. S. Kim and N. Roper and C. Seibert and M. Kelly and A. Lobanov and M. I. Aladjem and A. Luna and Y. Pommier},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.01.755884},
url = {https://www.biorxiv.org/content/10.64898/2026.10.01.755884v1},
note = {CC0},
}
RIS
TY - UNPB
TI - Dynamic Schlafen 11 (SLFN11) expression revealed by single-cell RNA sequencing of clonal human cancer cells
AU - D. Taniyama
AU - Y. Inoue
AU - F. Elloumi
AU - Y. S. Kim
AU - N. Roper
AU - C. Seibert
AU - M. Kelly
AU - A. Lobanov
AU - M. I. Aladjem
AU - A. Luna
AU - Y. Pommier
PY - 2026
DA - 2026/10/01
PB - bioRxiv
DO - 10.64898/2026.10.01.755884
UR - https://www.biorxiv.org/content/10.64898/2026.10.01.755884v1
AB - Schlafen 11 (SLFN11) is a key determinant of sensitivity to DNA-damaging therapies in multiple cancers including leukemia, Ewing sarcoma, head and neck cancers, mesothelioma and small cell lung cancer (SCLC). Here, utilizing immunofluorescence microscopy and single-cell RNA sequencing we characterized SLFN11 expression across eight different human cancer cell lines and found cell-to-cell heterogenous expression both at the protein and RNA levels. Gene set enrichment and pathway analyses show that SLFN11 is coexpressed with a distinct stress-response state and enhanced genome maintenance programs while being inversely correlated with protein translation pathways. Publicly available single-cell RNA-sequencing datasets of human SCLC tumors confirmed the heterogeneous distribution of SLFN11 expression and confirmed its association with replication-related transcriptional programs. These findings indicate that heterogeneous SLFN11 expression reflects dynamic regulation at the single-cell level. They also underscore the limitations of bulk proteomic and transcriptome profiling and point to a potential reservoir of intrinsic chemotherapy resistance.
ER -