GEO series

Identification of Novel Regulators of LINE-1 Expression via CRISPR/Cas9 Screening

GSE313499 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/12/12 Platform GPL21290

At a glance

RNA-seq (gene expression) · human · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 12 samples: 4 × HCT116-Cas9 no reporter vs 4 × HCT116-Cas9 L1 WT reporter vs 4 × HCT116-Cas9 L1 EN/RT MT reporterGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Identification of novel regulators of LINE-1 expression via CRISPR/Cas9 screeningMobile DNA · 2025

Summary (written by the submitters)

Background Long Interspersed Nuclear Elements-1 (LINE-1, L1) are transposable elements that make up roughly 17% of the human genome. These elements can copy and insert themselves into new genomic locations [1]. Typically, LINE-1 is repressed in healthy tissues but may become activated in various human diseases. LINE-1 expression has been associated with aging [2–4], neurodegenerative disorders [5–7], cancer [8–10], and autoimmune diseases [11,12].

Read the full summary ↓

Despite the strong association between LINE-1 expression and disease, the regulatory mechanisms controlling the expression of LINE-1-encoded ORF1p and ORF2p and the link between LINE-1 activity and cancer cell survival remain poorly understood. Gaining insights into these regulatory pathways may help elucidate how LINE-1 contributes to disease pathogenesis. Results To identify upstream regulators of LINE-1 and genes associated with LINE-1 activity-dependent lethality, we developed a dual-reporter system that simultaneously monitors the protein levels of LINE-1-encoded ORF1p and ORF2p (wild-type or catalytically inactive EN/RT mutant). Using genome-wide CRISPR/Cas9-based screens with this system, we identified candidate genes that may influence LINE-1 regulation at multiple levels, including RNA and protein expression. Alongside known factors such as the HUSH complex, the screens revealed additional genes not previously linked to LINE-1 regulation, suggesting possible new regulatory mechanisms for ORF1p and ORF2p expression. We also identified genes whose loss correlated with reduced viability in a manner dependent on LINE-1 activity. These findings collectively provide a broad resource for exploring cellular factors that may modulate LINE-1 expression and activity. Conclusion This study provides a resource for investigating the cellular regulation of LINE-1, highlighting distinct candidate factors that may modulate ORF1p and ORF2p expression and influence LINE-1 activity-associated cytotoxicity. While functional validation of these candidate regulators remains necessary, the findings offer a foundation for future studies aimed at experimentally confirming their roles and elucidating the molecular mechanisms underlying LINE-1 regulation and its potential contributions to disease contexts.

Published in

Identification of novel regulators of LINE-1 expression via CRISPR/Cas9 screening

Oksuz O, Chu C, Arisdakessian C et al. · Mobile DNA 2025 · PMID 41351057 · doi:10.1186/s13100-025-00386-5

This dataset

Open GSE313499 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE313499_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1379653 and SRA study SRP654579. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41351057) ↗

Study design

4 × HCT116-Cas9 no reporter vs 4 × HCT116-Cas9 L1 WT reporter vs 4 × HCT116-Cas9 L1 EN/RT MT reporter

Supports a between-group comparison across 12 samples.

How we read this: 3 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9369017 HCT116-Cas9 no reporter - Replicate-1 HCT116-Cas9 no reporter
GSM9369018 HCT116-Cas9 no reporter - Replicate-2 HCT116-Cas9 no reporter
GSM9369019 HCT116-Cas9 no reporter - Replicate-3 HCT116-Cas9 no reporter
GSM9369020 HCT116-Cas9 no reporter - Replicate-4 HCT116-Cas9 no reporter
GSM9369021 HCT116-Cas9 L1 WT reporter - Replicate-1 HCT116-Cas9 L1 WT repor…
GSM9369022 HCT116-Cas9 L1 WT reporter - Replicate-2 HCT116-Cas9 L1 WT repor…
GSM9369023 HCT116-Cas9 L1 WT reporter - Replicate-3 HCT116-Cas9 L1 WT repor…
GSM9369024 HCT116-Cas9 L1 WT reporter - Replicate-4 HCT116-Cas9 L1 WT repor…
GSM9369025 HCT116-Cas9 L1 EN/RT MT reporter - Replicate-1 HCT116-Cas9 L1 EN/RT MT…
GSM9369026 HCT116-Cas9 L1 EN/RT MT reporter - Replicate-2 HCT116-Cas9 L1 EN/RT MT…
GSM9369027 HCT116-Cas9 L1 EN/RT MT reporter - Replicate-3 HCT116-Cas9 L1 EN/RT MT…
GSM9369028 HCT116-Cas9 L1 EN/RT MT reporter - Replicate-4 HCT116-Cas9 L1 EN/RT MT…

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