Omics · study · 2026
Altered lipid metabolism contributes to cytopenia and myeloid expansion in parn-mutant dyskeratosis congenita
Listed in NCBI GEO
Germline mutations in the PARN gene cause dyskeratosis congenita, an inherited bone marrow failure syndrome (IBMFS) characterized by multilineage cytopenia and progression to myeloid disease.
Description
The mechanisms underlying this malignant transformation have not been fully elucidated. Using a loss-of-function zebrafish parn mutant generated through CRISPR-Cas9 editing, we found expanded myeloid progenitors and a loss of mature hematopoietic cells in mutant marrows.
Cholesterol biosynthesis was transcriptionally upregulated; a finding recapitulated in patient-derived iPSCs with PARN mutations. Further, we identified altered glycerophospholipid metabolism through untargeted lipidomics. Downstream, Erk/MAPK signaling was activated.
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Inhibiting cholesterol biosynthesis with either fatostatin or terbinafine hydrochloride rescued anemia in parn mutants. We propose that parn-mediated alterations in cholesterol and glycerophospholipid metabolism support the proliferation of immature hematopoietic cells through increased lipid raft stability and MAPK/Erk signaling. Inhibiting cholesterol biosynthesis may represent a novel treatment strategy to restore hematopoiesis and prevent the hyperproliferative evolution of this IBMFS.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305577 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305577 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1306567 ncbi.nlm.nih.gov/bioproject/PRJNA1306567 ↗
project · from NCBI GEO
Topics
- Stated by source
- Danio rerio · Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE305577 | 9 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| 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:7955 | 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 |