Centriolar Protein POC5 Regulates Human Adipogenesis and Cellular Senescence: Insights From a Novel Metabolic Ciliopathy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Centrosomes and primary cilia regulate cellular processes, including microtubule organization and lineage-specific differentiation. POC5, a core component of the centriolar inner scaffold, has been linked to syndromic ciliopathies, yet its role in adipose biology remains unclear. This study investigates the impact of POC5 deficiency on ciliary organization, cellular senescence, adipogenesis, and insulin signaling. To this end, we analyzed primary dermal fibroblasts from a patient carrying a novel homozygous p.(Gln206Ter) POC5 variant and performed mechanistic evaluations in human adipose stem cells (ASCs) with CRISPR-Cas9-mediated POC5 knockout. Centriolar architecture was examined using Ultrastructure Expansion Microscopy (U-ExM), and cellular phenotypes were assessed through proliferation, senescence, and signaling analyses. POC5-deficient fibroblasts showed marked disruption of centriolar architecture, including absent or abnormal primary cilia and supernumerary centrioles. These defects were associated with a 35% decrease in proliferation and a premature senescence, evidenced by increased SA-β-gal activity and upregulation of p-p53, p16, and p21. Moreover, insulin signaling was impaired, with reduced phosphorylation of IRβ, AKT, and ERK1/2. These phenotypes were recapitulated in POC5-KO ASCs, which additionally exhibited a near complete block of adipogenic differentiation,

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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