GEO series
Pooled CRISPR screens identify genes and non-coding genomic regions that regulate red blood cell density
GSE308629
Homo sapiens
Other; Expression profiling by high throughput sequencing
99 samples
Submitted 2026/08/07
Platform GPL24676
Summary
Genome-wide association studies have identified >1000 loci associated with clinically important red blood cell (RBC) traits, such as hemoglobin content and cell volume. However, few of these associations have been characterized at the molecular level such that most causal genes and variants remain elusive. Here, we performed pooled CRISPR screens in an erythroid cell line to identify genes and regulatory non-coding sequences that control RBC density. We perturbed 556 candidate genes and genomic sequences near 2114 GWAS variants. We used a density gradient to quantify the impact of these CRISPR perturbations on cell density. After validation, we found 17 genes and 13 regions near GWAS variants that regulate cell density. Some of these genes have previously been implicated in RBC biology (e.g. ATP2B4, CCND3, EPOR) although many are novel (e.g. CHTF8, CTU2, DNASE2). We confirmed that deletions in the osmotic stress response kinase gene OXSR1 increase cell density, and a phosphoproteome analysis in OXSR1-depleted cells indicated that this phenotype is accompanied with a dephosphorylation of the upstream kinase WNK1 and the downstream target KCC3 (SLC12A6). We also combined CRISPR perturbations and RNA-sequencing to show how a non-coding genomic sequence near rs13255015 regulates the expression of the transcription factor ZFAT in cis and SLC4A1 in trans. SLC4A1 encodes Band3, a known regulator of RBC hydration and volume. Our results suggest experimental strategies to characterize GWAS findings and provide new molecular insights into the regulation of complex RBC traits.
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE308629_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 99 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1331747 and SRA study SRP622532. Searching any of these in the dataset finder brings you back here.
Study design
8 conditions, mostly with about 5 replicates each
DS_Cas9_R1_fraction ×5
DS_Cas9_R2_fraction ×5
DS_Cas9_R3_fraction ×5
DS_Cas9_R4_fraction ×5
DS_KRAB_R1_fraction ×5
DS_KRAB_R2_fraction ×5
DS_KRAB_R3_fraction ×5
DS_KRAB_R4_fraction ×3
+2 more
Supports a between-group comparison across 38 samples.
8 replicated groups read from the first 40 of 99 sample titles; they account for 38 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9249414 DS_Plasmid_pHKO
- GSM9249415 DS_Plasmid_pMS2
- GSM9249416 DS_Cas9_R1_fraction_1
- GSM9249417 DS_Cas9_R1_fraction_2
- GSM9249418 DS_Cas9_R1_fraction_3
- GSM9249419 DS_Cas9_R1_fraction_4
- GSM9249420 DS_Cas9_R1_fraction_5
- GSM9249421 DS_Cas9_R2_fraction_1
- GSM9249422 DS_Cas9_R2_fraction_2
- GSM9249423 DS_Cas9_R2_fraction_3
- GSM9249424 DS_Cas9_R2_fraction_4
- GSM9249425 DS_Cas9_R2_fraction_5
- GSM9249426 DS_Cas9_R3_fraction_1
- GSM9249427 DS_Cas9_R3_fraction_2
- GSM9249428 DS_Cas9_R3_fraction_3
- GSM9249429 DS_Cas9_R3_fraction_4
- GSM9249430 DS_Cas9_R3_fraction_5
- GSM9249431 DS_Cas9_R4_fraction_1
- GSM9249432 DS_Cas9_R4_fraction_2
- GSM9249433 DS_Cas9_R4_fraction_3
- GSM9249434 DS_Cas9_R4_fraction_4
- GSM9249435 DS_Cas9_R4_fraction_5
- GSM9249436 DS_KRAB_R1_fraction_1
- GSM9249437 DS_KRAB_R1_fraction_2
- GSM9249438 DS_KRAB_R1_fraction_3
- GSM9249439 DS_KRAB_R1_fraction_4
- GSM9249440 DS_KRAB_R1_fraction_5
- GSM9249441 DS_KRAB_R2_fraction_1
- GSM9249442 DS_KRAB_R2_fraction_2
- GSM9249443 DS_KRAB_R2_fraction_3
- GSM9249444 DS_KRAB_R2_fraction_4
- GSM9249445 DS_KRAB_R2_fraction_5
- GSM9249446 DS_KRAB_R3_fraction_1
- GSM9249447 DS_KRAB_R3_fraction_2
- GSM9249448 DS_KRAB_R3_fraction_3
- GSM9249449 DS_KRAB_R3_fraction_4
- GSM9249450 DS_KRAB_R3_fraction_5
- GSM9249451 DS_KRAB_R4_fraction_1
- GSM9249452 DS_KRAB_R4_fraction_2
- GSM9249453 DS_KRAB_R4_fraction_3
+ 59 more — browse all 99 samples with per-sample file links →
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