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Heterogeneity in hematopoietic stem cell enables adaptation to the aged microenvironment [scRNA-seq]

GSE327449 Mus musculus (mouse) Single-cell RNA-seq 12 samples Submitted 2026/07/21 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 12 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
12 samples: 12 samples, each with a distinct title — no replicated groupsGroups 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
Transcriptional heterogeneity predicts and enables clonal selection in ageing haematopoiesisResearch square · 2026
Summary (written by the submitters)
Aging reshapes hematopoietic stem cell (HSC) behavior, yet how pre-existing heterogeneity forecasts clonal performance in aged microenvironments remains unclear. Using cellular barcoding and single cell-RNA-seq to longitudinally sample shared sister-clones across hetero- and homochronic transplants in mice, we quantify (i) intra- and inter-cellular transcriptional heterogeneity in young and old HSC, (ii) differential self-renewal and clonal fitness of HSC in reconstituted
Read the full summary ↓
hematopoiesis, and (iii) clone-wise associations between pre-existing programs and fitness in aging contexts via predictive machine learning models. Old HSC exhibit greater heterogeneity and rates of generation of heterogeneity, driven by specific gene sets with known roles in HSC fitness. Old HSC exhibit higher self-renewal in old relative to young hosts, likely reflecting adaptation over life to the aged altered niche. Clones with higher fitness in aged mice are enriched for signatures of quiescence, genome integrity/DNA repair, and inflammaging when compared to lower-fitness clones before transplantation. Pre-existing heterogeneity predicts both higher clone fitness and higher self-renewal in the old hosts after transplantation, providing greater phenotypic variability for selection of adaptive clones. Together, these data argue that intrinsic aging encodes variable clonal ‘starting positions’ that interact with niche age to shape hematopoietic output. Our results contextualize recent clonal tracing studies in native hematopoiesis and aging—where lineage output is clonally restricted and age-expanded clones persist—and extend them by prospectively linking baseline HSC state variation to subsequent fitness under aged conditions. These findings nominate actionable, pre-transplant molecular predictors of clonal performance and suggest strategies to modulate aging programs to rebalance hematopoiesis.
Published in
Transcriptional heterogeneity predicts and enables clonal selection in ageing haematopoiesis
De Dominici M, Qian K, Chen X et al. · Research square 2026 · PMID 42396490 · doi:10.21203/rs.3.rs-10046174/v1
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 GSE327449_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1450963 and SRA study SRP690454. Searching any of these in the dataset finder brings you back here.

Study design
12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. 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
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