GEO series
Setdb1 regulates proper differentiation of adult intestinal stem cells via restraining permissive chromatin structure and transcriptional variability
GSE279796
Mus musculus
Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing
18 samples
Submitted 2024/10/21
Platform GPL19057
Summary
The histone methylase Setdb1 plays a pivotal role in embryonic stem cell maintenance and developmental lineage specification. However, its function in adult stem cells remains elusive. Here we show that conditional inactivation of Setdb1 in Lgr5+ intestinal stem cells alters the transcriptional programs of the progeny cell types and results in increased cell-to-cell transcriptional variability. Loss of Setdb1 blocked differentiation towards the absorptive enterocyte lineage, while the generation of secretory cell types was only marginally affected due to the activation of alternative developmental trajectories. Setdb1 inactivation did not alter H3K9 methylation at large heterochromatin domains but led to reduced localized modifications at islands of gene-rich areas around transposase-accessible chromatin regions, which have doubled in number, became broader and more heterogeneous in size. The results demonstrate that Setdb1 regulates intestinal stem cell properties and epithelial lineage specification by limiting chromatin accessibility at open genomic areas and controlling cell-to-cell transcriptional variability.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE279796_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 18 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1174708 and SRA study SRP539356. Searching any of these in the dataset finder brings you back here.
Study design
18 conditions, each sampled once — no replicated groups
Read from 18 sample titles: 18 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM8580411 GFP_WT replicate 1, scRNA
- GSM8580412 GFP_WT replicate 2, scRNA
- GSM8580413 GFP_Setdb1KO replicate 1, scRNA
- GSM8580414 GFP_Setdb1KO replicate 2, scRNA
- GSM8580415 GFP_ WT, replicate 1 Total RNA-seq
- GSM8580416 GFP_ WT, replciate 2, Total RNA-seq
- GSM8580417 GFP_ Setdb1KO, replicate 1, Total RNA-seq
- GSM8580418 GFP_Setdb1KO, replicate 2, Total RNA-seq
- GSM8580419 GFP_WT_H3K9me3., replicate 1, ChIP
- GSM8580420 GFP_WT_H3K9me3., replicate 2, ChIP
- GSM8580421 GFP_Setdb1KO_H3K9me3., replicate 1, ChIP
- GSM8580422 GFP_Setdb1KO_Setdb1_H3K9me3., replicate 2, ChIP
- GSM8580423 GFP_WT , scATAC
- GSM8580424 GFP_Setdb1KO, scATAC
- GSM8580425 GFP_ WT nTnG, replicate 1, scRNA
- GSM8580426 GFP_ WT nTnG, replicate 2, scRNA
- GSM8580427 GFP_ Setdb1-KO nTnG, replicate 1, scRNA
- GSM8580428 GFP_ Setdb1-KO nTnG, replicate 2, scRNA
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