H3K18 lactylation-hexokinase 2 positive feedback loop promotes osteogenesis of ASPCs in facial infiltrating lipomatosis.

ABSTRACT:

Background

Facial infiltrating lipomatosis (FIL) is a rare congenital disorder characterized by adipose hyperplasia and osseous overgrowth, driven by somatic PIK3CA mutations. While PIK3CA-induced metabolic reprogramming elevates lactate levels, the role of histone lactylation in FIL pathogenesis remains unclear.

Methods

Adipose stem and progenitor cells (ASPCs) from FIL adipose tissue were isolated. Glycolysis inhibitors (2-DG, oxamate), lactate supplementation, and siRNA-mediated knockdown were used to modulate lactylation. CUT&Tag sequencing, Western blot, qPCR, ChIP-qPCR and functional assays (osteogenic/adipogenic differentiation) were performed to elucidate the potential mechanism.

Results

FIL-ASPCs exhibited hyperlactylation, particularly at H3K18. H3K18la prom

SUBMITTER: Chen H 

PROVIDER: S-EPMC12486737 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature