GEO series

SLF2 and SMC5 dysfunction drives HSC aging and predisposes to MDS, defining a new inherited bone marrow failure syndrome [RNA-seq]

GSE316081 Homo sapiens (human) RNA-seq (gene expression) 6 samples Submitted 2026/08/06 Platform GPL30173

At a glance

RNA-seq (gene expression) · human · 6 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: 6 samples: 3 × mutant #1 vs 3 × corrected #Groups 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.

Summary (written by the submitters)

Pathogenic variants in SLF2 and SMC5 cause a developmental disorder known as Atelis Syndrome, characterized by microcephaly, short stature, and hematological abnormalities, most notably anemia and lymphopenia. However, its clinical relevance to hematology has not yet been established, and the underlying pathogenic mechanisms remain largely unknown.

Read the full summary ↓

Prompted by our longitudinal follow-up and re-evaluation revealing that some patients with Atelis Syndrome developed myelodysplastic syndromes (MDS) or MDS-like features, we elucidated the hematopoietic defects using hematopoietic stem and progenitor cells (HSPCs) derived from patient-specific induced pluripotent stem cells carrying compound heterozygous SLF2 mutations (mutant HSPCs) and gene-corrected isogenic controls. Mutant HSPCs exhibited impaired colony-forming capacity and defective erythroid differentiation with a myeloid bias. Crucially, in vivo xenotransplantation revealed that mutant HSPCs had significantly reduced long-term engraftment capacity. Knockdown of SMC5 in human cord blood CD34+ cells similarly impaired colony formation. Mechanistically, disruption of the SLF2–SMC5 axis induces increased genomic instability, p53/p21 activation, and transcriptional signatures of senescence. Furthermore, ATAC sequencing uncovered epigenetic features of hematopoietic stem cell (HSC) aging, including increased accessibility at PU.1 motifs, driving myeloid bias. In conclusion, we establish that SLF2 and SMC5 dysfunction drives premature HSC aging and predisposes to MDS, defining Atelis Syndrome as a distinct entity within the inherited bone marrow failure syndromes (IBMFS). These findings highlight the need to incorporate Atelis Syndrome into the diagnostic framework of IBMFS, improving genetic diagnosis and guiding clinical management of hematological abnormalities.

This dataset

Open GSE316081 in finder → Find more human RNA-seq datasets → Myelodysplastic syndromes landscape →

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 GSE316081_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 PRJNA1400557 and SRA study SRP661054. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × mutant #1 vs 3 × corrected #

Supports a between-group comparison across 6 samples.

How we read this: 2 replicated groups read from 6 sample titles; they account for 6 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

GSM9444278 mutant #1-1 mutant #1
GSM9444279 mutant #1-2 mutant #1
GSM9444280 mutant #1-3 mutant #1
GSM9444281 corrected #2 corrected #
GSM9444282 corrected #3 corrected #
GSM9444283 corrected #1 corrected #

More Myelodysplastic syndromes datasets

GSE316079 SLF2 and SMC5 dysfunction drives HSC aging and predisposes to MDS, defining a new inherited bone marrow failure syndrome [ATAC-seq] 6 samples same disease briefing · shares slf2, smc5, hsc, mds, dysfunction, predisposes, inherited, defining
GSE264117 Investigating microenvironment in MDS II 503 samples same disease briefing · shares mds
GSE281562 Unique epigenomic signatures identify biologically significant subtypes of MDS and predict response to azacytidine [RNA-Seq] 83 samples same disease briefing · shares mds
GSE211032 Expression Analysis (RNA-Seq) of adult Myelodysplastic Syndromes (MDS)/Acute Myeloid Leukemia (AML) with isolated monosomy 7 compared to controls 45 samples same disease briefing · shares mds
GSE288862 ScRNA-Seq of Human MDS and AML Bone Marrow Marrow Microenvironment. 3 samples same disease briefing · shares mds
GSE284647 The genotype-integrated gene expression profile at the single-cell level of bone marrow CD34-positive hematopoietic stem and progenitor cells (HSPCs) from a patient with myelodysplastic neoplasms (MDS) harboring germline and somatic DDX41 variants. 1 samples same disease briefing · shares mds
GSE298020 PU.1-Activated Genomic Regions Define Low-risk MDS Subsets Characterized by Immune Dysregulation and Disease Progression. 493 samples same disease briefing · shares mds
GSE275000 Clinical response to azacitidine in MDS is associated with distinct DNA methylation changes in HSPCs 104 samples same disease briefing · shares mds

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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.