Omics · study · 2026
Metabolic checkpoint controls hematopoietic stem cell replicative lifespan (Bulk RNA-Seq)
Listed in NCBI GEO
Adult hematopoietic stem cells (HSCs) sustain the lifelong production of all mature blood and immune cells.
Description
HSCs possess extensive regenerative potential, but the actual self-renewal of HSCs is limited. A long-standing question has been why replicative history negatively impacts HSC lineage-generating capacity.
We found that accrued divisions durably alter HSC production; generating low-output bone-marrow landscapes that are highly variable in both lineage contribution and transcriptional divergence within individual lineages. Mechanistically, division-driven functional alterations in HSCs are due to redirecting branched chain amino acid (BCAA) usage from catabolic towards anabolic activity, causing faster HSC cell-cycle kinetics.
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Adding a BCAA deaminated product is sufficient to bypass the BCAA catabolic checkpoint and slow down the cell cycle, durably rescuing balanced lineage output of HSCs with accrued divisions. Hence, our study suggests a novel paradigm whereby replicative history causes metabolic and transcriptional drift, generating divergent HSC output. Division-dependent HSC functional drift can be restored by metabolite replacement, which has long-term therapeutic implications for HSC regenerative medicine.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE256nnn/GSE256529 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE256529 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1079833 ncbi.nlm.nih.gov/bioproject/PRJNA1079833 ↗
project · from NCBI GEO
- PubMed 41534523 pubmed.ncbi.nlm.nih.gov/41534523 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- RNA sequencing 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE256529 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| 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[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| 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 |