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Omics · study · 2026

m6Am methyltransferase PCIF1 regulates osteogenesis via WNT signaling

Listed in NCBI GEO

Skeletal development depends on the self-renewal and differentiation of MSCs.

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Emerging research underscores the regulatory functions of RNA methylation on bone homeostasis. Here, we show PCIF1, the N6,2′-O-dimethyladenosine (m6Am) methyltransferase, is essential for maintaining bone mass and promoting osteogenic differentiation of MSCs.

Multiple complementary analyses—including GWAS, TWAS, and single-cell transcriptomics—collectively point to PCIF1 as a regulator of human bone mineral traits and a marker of early mesenchymal stem cells. Global or MSC-specific Pcif1 deletion elicits osteoporotic pathology in mice, although myeloid cell-specific Pcif1 knockout does not induce femur bone alternation alterations. Mechanistically, Pcif1 knockout decreases m6Am signals of Wnt-related genes (Wnt11, Fzd4, Fgfr2) and accelerates mRNA degradation.

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This down-regulates active β-Catenin protein, and thus impairs osteogenic function of MSCs. Additionally, the WNT agonist attenuates the osteoporosis-like phenotype induced by Pcif1 deletion. These findings highlight the crucial role of PCIF1-mediated m6Am modification in regulating osteogenesis and suggest potential therapeutic implications for bone disorders.

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Provenance · 1 source records, 7 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE32499813 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title