GEO series
Independent cell type-specific expression and distal regulation of the 9p21 locus cell cycle regulators: p14ARF, p16INK4A, p15INK4A, and ANRIL [CRISPR and scRNA-seq]
GSE309511
Homo sapiens
Other; Expression profiling by high throughput sequencing
32 samples
Submitted 2026/06/29
Platform GPL18573
Summary
The 9p21 locus encodes tumor suppressors p16INK4A and p14ARF (both encoded by CDKN2A), p15INK4B (CDKN2B), and a long non-coding RNA, ANRIL (CDKN2B-AS1). The ~1 megabase locus is notable for a high density of single nucleotide polymorphisms (SNPs) associated with aging-related diseases and traits. Despite clear importance, our understanding of the the cell-type specific expression dynamics and cis-regulatory mechanisms of the 9p21 transcripts has been constrained by the complexity of the transcript structures, low expression, and severe alterations to the locus in cancer cell lines. Here, we innovated custom computational and molecular tools to overcome these technical challenges and fill critical knowledge gaps in our understanding of 9p21 locus architecture and regulation of the 9p21 transcripts. Across tissues, we found that p15INK4b is the predominant transcript. We deconvolved the expression of the CDKN2A transcripts, p16INK4A and p14ARF, revealing stark differences in the expression of these overlapping but functionally distinct transcripts across tissues and cell types. Comparative analysis in a model of fibroblast senescence revealed a striking switch from preferential p14ARF expression in cycling cells, to p16INK4A and p15INK4b as cells age and senescence. Perturbation of putative cis regulatory elements nominated a network of promoters and enhancers that regulate p16INK4A, p14ARF, and p15INK4b and ANRIL. The identified elements are accessible in vivo, and can be used to guide studies into variant interpretation. Our systematic characterization of 9p21 transcript isoforms, promoters, and distal elements across cell states, in vivo tissues and senescence offers new mechanistic insights and a framework for future studies of this vital but poorly understood locus.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE309511_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 32 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1336192 and SRA study SRP629597. Searching any of these in the dataset finder brings you back here.
Study design
16 × CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array vs 16 × CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array
Supports a between-group comparison across 32 samples.
2 replicated groups read from 32 sample titles; they account for 32 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9268463 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array1
- GSM9268464 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array1
- GSM9268465 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array2
- GSM9268466 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array2
- GSM9268467 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array3
- GSM9268468 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array3
- GSM9268469 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array4
- GSM9268470 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array4
- GSM9268471 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array5
- GSM9268472 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array5
- GSM9268473 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array6
- GSM9268474 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array6
- GSM9268475 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array7
- GSM9268476 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array7
- GSM9268477 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array8
- GSM9268478 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array8
- GSM9268479 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array9
- GSM9268480 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array9
- GSM9268481 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array10
- GSM9268482 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array10
- GSM9268483 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array11
- GSM9268484 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array11
- GSM9268485 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array12
- GSM9268486 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array12
- GSM9268487 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array13
- GSM9268488 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array13
- GSM9268489 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array14
- GSM9268490 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array14
- GSM9268491 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array15
- GSM9268492 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array15
- GSM9268493 CRISPRa screen and dial-up scRNA-seq, WI-38 fibroblasts, array16
- GSM9268494 CRISPRa screen mRNA scRNA-seq, WI-38 fibroblasts, array16
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