GEO series

Senescent cells cluster CTCF on nuclear speckles to sustain their splicing program [RNA-seq]

GSE269856 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2024/06/17 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 14 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: 14 samples: 7 conditions, mostly in duplicateGroups 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.

Summary (written by the submitters)

Senescence —the end-point of the replicative life span of normal cells— is characterized by a complex sequence of molecular and biochemical events. One of these is the dramatic reorganization of CTCF into large senescence-induced CTCF clusters (SICCs). However, the molecular determinants, genomic consequences, and functional purpose of SICCs remained unknown.

Read the full summary ↓

Here, we combine super-resolution imaging, 3D genomics, and functional assays with computational modelling to address all aspects of SICC emergence. First, we used modelling and data from the overexpression of nuclear factors lost upon senescence entry to explain how changes in the nuclear environment allow for CTCF clustering. Second, we discovered that cells entering senescence repurpose SRRM2 —a key component of nuclear speckles— and BANF1 —a protein known to act as ‘molecular glue’ for chromosomes during mitosis— to cluster CTCF on the surface of speckles, while rewiring higher-order genome architecture. Last, we could show that SICCs are required for the faithful execution of the senescence splicing program as their disruption by SRRM2 or BANF1 depletion reverts splicing choices. Together, the senescence-specific clustering of CTCF on nuclear speckles is a new paradigm of a change in the biochemical environment of the nucleus being translated into its architectural reorganization to allow for the deployment of a splicing program driving homeostatic deregulation.

This dataset

Open GSE269856 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 GSE269856_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 PRJNA1124022 and SRA study SRP513944. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

7 conditions, mostly in duplicate

IMR90, wild type, RNA-seq, ×2 IMR90, siHMGB2, RNA-seq, ×2 IMR90, ICM, RNA-seq, ×2 IMR90, siSRRM2, RNA-seq, ×2 IMR90, siBANF1, RNA-seq, ×2 IMR90, ICM, ×2 IMR90, siCTCF, ×2

Supports a between-group comparison across 14 samples.

How we read this: 7 replicated groups read from 14 sample titles; they account for 14 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

GSM8328987 IMR90, wild type, RNA-seq, replicate 1 IMR90, wild type, RNA-s…
GSM8328988 IMR90, wild type, RNA-seq, replicate 2 IMR90, wild type, RNA-s…
GSM8328989 IMR90, siHMGB2, RNA-seq, replicate 1 IMR90, siHMGB2, RNA-seq,
GSM8328990 IMR90, siHMGB2, RNA-seq, replicate 2 IMR90, siHMGB2, RNA-seq,
GSM8328991 IMR90, ICM, RNA-seq, replicate 1 IMR90, ICM, RNA-seq,
GSM8328992 IMR90, ICM, RNA-seq, replicate 2 IMR90, ICM, RNA-seq,
GSM8328993 IMR90, siSRRM2, RNA-seq, replicate 1 IMR90, siSRRM2, RNA-seq,
GSM8328994 IMR90, siSRRM2, RNA-seq, replicate 2 IMR90, siSRRM2, RNA-seq,
GSM8328995 IMR90, siBANF1, RNA-seq, replicate 1 IMR90, siBANF1, RNA-seq,
GSM8328996 IMR90, siBANF1, RNA-seq, replicate 2 IMR90, siBANF1, RNA-seq,
GSM8607128 IMR90, ICM, replicate 3 IMR90, ICM,
GSM8607129 IMR90, ICM, replicate 4 IMR90, ICM,
GSM8607130 IMR90, siCTCF, replicate 1 IMR90, siCTCF,
GSM8607131 IMR90, siCTCF, replicate 2 IMR90, siCTCF,

Datasets on a similar topic

GSE284194 Senescent cells cluster CTCF on nuclear speckles to sustain their splicing program 34 samples shares ctcf, senescent, speckles, splicing, cluster, nuclear, sustain, program
GSE217753 DNA methylation insulates exons from CTCF loops with nuclear speckles (CUT&TAG) 14 samples shares ctcf, speckles, nuclear
GSE285077 Chromatin-associated lncRNA-splicing factor condensates regulate hypoxia responsive RNA processing of genes pre-positioned near nuclear speckles [RNA-seq] 76 samples shares speckles, splicing, nuclear
GSE285088 Chromatin-associated lncRNA-splicing factor condensates regulate hypoxia responsive RNA processing of genes pre-positioned near nuclear speckles [eCLIP-seq] 24 samples shares speckles, splicing, nuclear
GSE248102 CTCF/cohesin organize the ground state of chromatin-nuclear speckle association [RNA-Seq] 59 samples shares ctcf, nuclear
GSE239270 Investigate FOXA2, NKX2-1, CTCF and P300 cistrome and enhancer (H3K27ac and H3k4me1) reprogramming during NEPC transformation by ChIP-seq. 104 samples shares ctcf, program
GSE341599 CTCFL(BORIS) contributes to the transcriptional program of ovarian cancer by relaxing CTCF-mediated three-dimensional genome organization 32 samples shares ctcf, program
GSE216843 Hypoxia-induced CTCF mediates alternative splicing via coupling chromatin looping and RNA Pol II pause to promote EMT in breast cancer 18 samples shares ctcf, splicing

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