GEO series

Temporal and Clonal Resolution of Cellular Evolution Under Stress

GSE305751 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing 42 samples Submitted 2026/08/01 Platform GPL30173Platform GPL18573

Summary

Dissecting cellular evolution under transient versus persistent stress is essential for understanding both healthy and pathological processes. Yet cellular stress responses involve nonlinear dynamics and survival bottlenecks, making them challenging to study. We develop a framework that combines single-cell multiomic lineage tracing with statistical modeling to quantify how individual cells contribute to the future population, by explicitly modeling exponential expansion and intra-clonal heterogeneity. Applied to a cancer model under short- and long-term treatment, we identify clones primed to endure treatment versus ones that survive by producing diverse progeny, enabling characterization of molecular features enriched in each clonal survival strategy. This framework can quantify treatment-driven selection and adaptation, revealing that their relative contributions to population dynamics vary between treatments. Furthermore, short- and long-term treatment results in expansion of distinct clones characterized by different gene programs and transcription factor activity. Notably, certain pathways such as AP-1 signaling can limit initial cancer cell growth but promote later resistance, and such opposing associations are consistently observed in independent experiments and clinical data. Together, this study introduces a generalizable approach for investigating cellular evolution in a time- and clone-resolved manner, and highlights time-dependent molecular programs that underlie stress responses.

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Direct links to NCBI, no account and no request form: the whole study as GSE305751_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 42 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1307552 and SRA study SRP609694. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

13 conditions, mostly in triplicate

Day0_scMulti_GEX_2022_04 ×3 Day10_DABTRAM_scMulti_GEX_2022_04 ×3 Day10_COCL2_scMulti_GEX_2022_04 ×3 Day10_CIS_scMulti_GEX_2022_04 ×3 Week5_DABTRAM_scMulti_GEX_2022_04 ×3 Week5_COCL2_scMulti_GEX_2022_04 ×3 Week5_CIS_scMulti_GEX_2022_04 ×3 Day0_scMulti_ATAC_2022_05 ×2 +12 more

Supports a between-group comparison across 33 samples.

13 replicated groups read from the first 40 of 42 sample titles; they account for 33 of them. Check it against the sample list below before relying on it.

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