GEO series

Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans (Human Bulk RNA-Seq)

GSE277682 Homo sapiens (human) RNA-seq (gene expression) 11 samples Submitted 2026/07/22 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 11 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: 11 samples: 7 × SCD vs 4 × NSGroups 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: Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humansScience translational medicine · 2026

Summary (written by the submitters)

Curative therapies using autologous genetically modified hematopoietic stem and progenitor cells (HSPCs) are now FDA-approved for sickle cell disease (SCD). However, there are concerns that the pathophysiology of SCD may degrade the quality of HSPCs required for these cellular therapies. We interrogated the phenotype and function of HSPCs in mice and individuals with SCD.

Read the full summary ↓

We observed elevated cycling, DNA damage, reactive oxygen species, and hallmarks of senescence in bone marrow HSPCs from SCD mice, which correlated with a loss of long-term repopulating HSPCs. Bone marrow HSPCs from individuals with SCD also display hallmarks of senescence and diminished function. Transcriptomic profiling of mouse and human HSPCs revealed reduced expression of genes regulating cell cycle, DNA replication, and DNA repair, consistent with senescence. Treatment of SCD mice with the senolytic, ABT-263 (Navitoclax), increased HSPC frequency, restored HSPC transplantation activity, and decreased numbers of HSPCs with DNA damage. Thus, we demonstrate that stress-associated loss of function in the bone marrow of mice and individuals with SCD is reversible with senolytic therapy. Our work suggests a strategy for improving the function and fidelity of HSPCs collected for autologous gene therapy, which could further improve the efficacy and safety of these curative therapies.

Published in

Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans

Barve A, Dabas P, Cornwell A et al. · Science translational medicine 2026 · PMID 42485438 · doi:10.1126/scitranslmed.adv0628

This dataset

Open GSE277682 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 GSE277682_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 PRJNA1163348 and SRA study SRP533868. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42485438) ↗

Study design

7 × SCD vs 4 × NS

Supports a between-group comparison across 11 samples.

How we read this: 2 replicated groups read from 11 sample titles; they account for 11 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

GSM8527561 NS8 NS
GSM8527562 NS3 NS
GSM8527563 NS5 NS
GSM8527564 NS9 NS
GSM8527565 SCD7 SCD
GSM8527566 SCD3 SCD
GSM8527567 SCD2 SCD
GSM8527568 SCD11 SCD
GSM8527569 SCD12 SCD
GSM8527570 SCD13 SCD
GSM8527571 SCD1 SCD

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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.