PTEN regulates adipose progenitor cell growth, differentiation, and replicative aging

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• PTEN (phosphatase and tensin homolog) is a tumor suppressor regulating insulin signaling.
• Germline PTEN variants cause PTEN hamartoma tumor syndrome (PHTS), linked to childhood lipomas.
• Adipose progenitor cells (APCs) from PHTS patients show sustained adipogenic potential, unlike controls.

Purpose of the Study:

• Investigate PTEN's role in adipose tissue development and aberrant growth.
• Elucidate mechanisms linking PTEN loss to enhanced adipogenesis and PHTS.
• Determine PTEN's influence on APC proliferation, differentiation, and senescence.

Main Methods:

• Functional assays and RNA-Seq on control and PTEN-knockdown APCs.
• PTEN reduction using siRNA and CRISPR gene editing.
• Overexpression of constitutively active FOXO1 in PTEN-edited cells.

Main Results:

• PTEN knockdown increased APC proliferation and differentiation.
• FOXO1 (Forkhead box protein O1) phosphorylation increased, upregulating SREBP1 (sterol regulatory element-binding protein 1) and enhancing lipogenesis.
• PTEN-deficient cells exhibited reduced senescence, with downregulated CDKN1A (p21).

Conclusions:

• PTEN negatively regulates APC proliferation, differentiation, and senescence.
• Loss of PTEN function promotes adipogenesis via FOXO1/SREBP1 pathway dysregulation.
• PTEN's role in APC senescence and proliferation contributes to adipose tissue abnormalities in PHTS.