Omics · study · 2026
Metabolite-induced DNA damage drives stochastic stem cell loss and clonal hematopoiesis
Listed in NCBI GEO
DNA damage and mutations in hematopoietic stem cells (HSC) enable clonal hematopoiesis (CH).
Description
Such damage occurs throughout life, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH.
We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial from embryonic HSC emergence and throughout life. Despite a severe deficiency in HSCs, these mice produce blood for many months.
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To determine what enables this, we employed a new unbiased method for detecting clones which exploits somatic variant data. This revealed initial polyclonal hematopoiesis which diminishes to monoclonal CH, devoid of known genetic selection. Furthermore, in FA children, we find the same transition to monoclonal hematopoiesis.
Therefore, DNA damage-induced attrition down to a last functional cell can be a driving force for CH, representing an alternative route to CH other than purely by fitness-enhancing selection.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316966 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316966 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1405608 ncbi.nlm.nih.gov/bioproject/PRJNA1405608 ↗
project · from NCBI GEO
- PubMed 41875892 pubmed.ncbi.nlm.nih.gov/41875892 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 70%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE316966 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (70%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |