GEO series
Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromes
GSE292039
Homo sapiens (human)
RNA-seq (gene expression)
27 samples
Submitted 2025/06/23
Platform GPL24676Platform GPL18573
At a glance
RNA-seq (gene expression) · human · 27 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)
- Topic
- Myelodysplastic syndromesThis series is part of our curated briefing on it.
- Samples
- 27 samples: 8 × Medalist trial patient Responderj1376_samp vs 6 × Medalist trial patient Responderj1383_samp vs 5 × Medalist trial patient Non-responderj1375_sampGroups 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
- Splicing of erythroid transcription factor is associated with therapeutic response in myelodysplastic syndromesThe Journal of clinical investigation · 2025
Summary (written by the submitters)
Anemia is the primary clinical manifestation of myelodysplastic syndromes (MDS), but the molecular pathogenesis of ineffective erythropoiesis remains incompletely understood. Luspatercept, an activin receptor 2B (ACVRIIB-Fc) ligand trap, has been approved to treat anemia, however its molecular mechanism of action is unclear. We found that the ACVR2B, its ligand GDF11, and effector, SMAD2, are upregulated in MDS patient samples.
Read the full summary ↓
GDF11 inhibited human erythropoiesis in vitro and caused anemia in zebrafish, effects that were abrogated by luspatercept. Upon GDF11 stimulation of human erythroid progenitors, SMAD2 binding occurred in the erythroid regulatory regions, including at GATA1 intron. Intronic SMAD2 binding led to skipping of exon 2 of GATA1, resulting in a shorter, hypomorphic isoform (GATA1s). CRISPR deletion of the SMAD2 binding intronic region decreased GATA1s production upon GDF11 stimulation. Expression of gata1s in a mouse model led to anemia,rescued by a murine ActRIIB-Fc (RAP-536). Finally, RNA-seq analysis of samples from the Phase 3 MEDALIST trial revealed that responders to Luspatercept had a higher proportion of GATA1s compared to non-responders. Moreover, the increase RBCs post-treatment was linked to a relative decrease in GATA1s isoform. Our study indicates that GDF11-mediated SMAD2 activation results in an increase in functionally impaired GATA1 isoforms, consequently contributing to anemia and influencing responses to Luspatercept in MDS.
Published in
Aluri S, Ling T, Fraint E et al.
· The Journal of clinical investigation 2025
· PMID 40424086
· doi:10.1172/JCI189266
This dataset
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.
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 GSE292039_RAW.tar (it can run to tens of gigabytes).
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.
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 PRJNA1236366 and SRA study SRP570538. Searching any of these in the dataset finder brings you back here.
Study design
8 × Medalist trial patient Responderj1376_samp vs 6 × Medalist trial patient Responderj1383_samp vs 5 × Medalist trial patient Non-responderj1375_samp
Supports a between-group comparison across 19 samples.
How we read this: 3 replicated groups read from 27 sample titles; they account for 19 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
- GSM8846857 CD34+ d6 erythroid progenitors treated with vehiclej972_rna_d6C.ATCACG.J972.AHJ5M5BGX7.L1-4.1
- GSM8846858 CD34+ d6 erythroid progenitors treated with GDF11j972_rna_d6G.TAGCTT.J972.AHJ5M5BGX7.L1-4.1
- GSM8846859 CD34+ d6 erythroid progenitors treated with vehiclej1469_rna_7_S7
- GSM8846860 CD34+ d6 erythroid progenitors treated with GDF11j1469_rna_8_S8
- GSM8846861 Medalist trial patient Non-responderj1375_samp10 Medalist trial patient …
- GSM8846862 Medalist trial patient Non-responderj1375_samp11 Medalist trial patient …
- GSM8846863 Medalist trial patient Non-responderj1375_samp12 Medalist trial patient …
- GSM8846864 Medalist trial patient Non-responderj1375_samp13 Medalist trial patient …
- GSM8846865 Medalist trial patient Non-responderj1375_samp9 Medalist trial patient …
- GSM8846866 Medalist trial patient Non-responderj1422_sampA1
- GSM8846867 Medalist trial patient Non-responderj1422_sampC1
- GSM8846868 Medalist trial patient Non-responderj1422_sampD1
- GSM8846869 Medalist trial patient Responderj1422_sampE1
- GSM8846870 Medalist trial patient Responderj1376_samp1 Medalist trial patient …
- GSM8846871 Medalist trial patient Responderj1376_samp2 Medalist trial patient …
- GSM8846872 Medalist trial patient Responderj1376_samp3 Medalist trial patient …
- GSM8846873 Medalist trial patient Responderj1376_samp4 Medalist trial patient …
- GSM8846874 Medalist trial patient Responderj1376_samp5 Medalist trial patient …
- GSM8846875 Medalist trial patient Responderj1376_samp6 Medalist trial patient …
- GSM8846876 Medalist trial patient Responderj1376_samp7 Medalist trial patient …
- GSM8846877 Medalist trial patient Responderj1376_samp8 Medalist trial patient …
- GSM8846878 Medalist trial patient Responderj1383_samp21 Medalist trial patient …
- GSM8846879 Medalist trial patient Responderj1383_samp23 Medalist trial patient …
- GSM8846880 Medalist trial patient Responderj1383_samp31 Medalist trial patient …
- GSM8846881 Medalist trial patient Responderj1383_samp33 Medalist trial patient …
- GSM8846882 Medalist trial patient Responderj1383_samp35 Medalist trial patient …
- GSM8846883 Medalist trial patient Responderj1383_samp37 Medalist trial patient …
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Share this dataset
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.