GEO series

Inhibition of NLRP1 Inflammasome Activation by Tyrosine Kinase Inhibitors Restores Erythropoiesis in Diamond-Blackfan Anemia Syndrome

GSE300483 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/09/01 Platform GPL30173

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: 3 × K562 Mock DMSO replica vs 3 × K562 Hemin DMSO replica vs 3 × K562 Mock Nilotinib replica vs 3 × K562 Hemin Nilotinib replicaGroups 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: TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndromeEMBO molecular medicine · 2026

Summary (written by the submitters)

Diamond-Blackfan Anemia Syndrome (DBAS) is characterized by impaired erythropoiesis due to dysfunctional ribosome biogenesis and aberrant cellular signaling. Here, we investigate how ribosomal stress-induced activation of the NLRP1 inflammasome modulates erythroid differentiation in DBAS. We demonstrate that FDA/EMA-approved tyrosine kinase inhibitors (TKIs) effectively mitigate defective erythropoiesis in Diamond-Blackfan anemia syndrome (DBAS) by inhibiting NLRP1 inflammasome activation.

Read the full summary ↓

Specifically, nilotinib enhances erythroid differentiation in K562 cells through suppression of the ZAKα/P38/NLRP1/CASP1 axis, leading to increased GATA1 protein levels and upregulation of key erythroid genes involved in iron acquisition, hemoglobin synthesis, and erythrocyte structure. These effects were validated in human CD34+ hematopoietic stem and progenitor cells (HSPCs) and zebrafish models, where nilotinib, along with other TKIs (imatinib, dasatinib, and bosutinib), promoted erythropoiesis at the expense of myelopoiesis and reduced caspase-1 activity. Importantly, in RPS19-deficient zebrafish and human models and HSPCs from patients with DBAS, nilotinib, imatinib and dasatinib rescued defective erythroid differentiation and restored hemoglobin levels. These findings highlight the potential of TKIs to address the erythroid defects observed in ribosomopathies like DBAS. Given the limited treatment options available for DBAS and other congenital anemias, our study provides compelling evidence for repurposing TKIs as a novel therapeutic strategy to alleviate pathological NLRP1 activation and improve erythropoiesis. This work opens new avenues for managing ribosome-related disorders and advancing personalized medicine approaches for hematopoietic diseases.

Published in

TKI-mediated inhibition of NLRP1 inflammasome restores erythropoiesis in DBA syndrome

Lozano-Gil JM, Rodríguez-Ruiz L, Palacios M et al. · EMBO molecular medicine 2026 · PMID 41514124 · doi:10.1038/s44321-025-00368-3

This dataset

Open GSE300483 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 GSE300483_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 PRJNA1281036 and SRA study SRP594028. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41514124) ↗

Study design

3 × K562 Mock DMSO replica vs 3 × K562 Hemin DMSO replica vs 3 × K562 Mock Nilotinib replica vs 3 × K562 Hemin Nilotinib replica

Supports a between-group comparison across 12 samples.

How we read this: 4 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

GSM9062047 K562 Mock DMSO replica1 K562 Mock DMSO replica
GSM9062048 K562 Mock DMSO replica2 K562 Mock DMSO replica
GSM9062049 K562 Mock DMSO replica3 K562 Mock DMSO replica
GSM9062050 K562 Hemin DMSO replica1 K562 Hemin DMSO replica
GSM9062051 K562 Hemin DMSO replica2 K562 Hemin DMSO replica
GSM9062052 K562 Hemin DMSO replica3 K562 Hemin DMSO replica
GSM9062053 K562 Mock Nilotinib replica1 K562 Mock Nilotinib rep…
GSM9062054 K562 Mock Nilotinib replica2 K562 Mock Nilotinib rep…
GSM9062055 K562 Mock Nilotinib replica3 K562 Mock Nilotinib rep…
GSM9062056 K562 Hemin Nilotinib replica1 K562 Hemin Nilotinib re…
GSM9062057 K562 Hemin Nilotinib replica2 K562 Hemin Nilotinib re…
GSM9062058 K562 Hemin Nilotinib replica3 K562 Hemin Nilotinib re…

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.