Effects of Notch signaling on proliferation, angiogenesis, and adipogenesis of hemangioma-derived stem cells
Year: 2025
Type: article
Abstract: Hemangioma-derived stem cells (Hem-SCs) constitute the cellular basis for adipogenesis during infantile hemangioma (IH) regression, with Notch signaling implicated in this process. To elucidate Notch's role in Hem-SCs biology, we isolated primary Hem-SCs from proliferative-phase IH specimens and validated their stem cell characteristics. Three days post-intervention with the γ-secretase inhibitor DAPT (N‑[N‑(3,5‑difluorophenacetyl)‑L‑alanyl]‑S‑phenylglycine t‑butylester), we assessed Notch and PI3K/AKT signaling dynamics while concurrently measuring vascular endothelial growth factor receptor (VEGFR) protein expression. Cellular proliferation was quantified via CCK-8 assay. During adipogenic differentiation (Day 14), RTqPCR evaluated Notch pathway genes (Notch1, Jagged1, Hes1), while adipogenic commitment was determined through Oil Red O staining and adipocyte-specific gene expression (PPARγ, C/EBPα). We demonstrate that DAPT suppresses Notch and PI3K/AKT signaling in Hem-SCs, concomitantly enhancing cellular proliferation and angiogenesis. Simultaneous analysis of VEGFR expression revealed differential DAPT-mediated regulation: VEGFR1 downregulation with concomitant VEGFR2 upregulation. During adipogenic induction, Notch pathway genes (Notch1, Jagged1, Hes1) were significantly downregulated. DAPT treatment further elevated adipogenic markers (PPARγ, C/EBPα) and lipid accumulation. Crucially, co-administration of the PI3K activator 740Y-P reversed DAPT-induced adipogenesis. Mechanistically, Notch inhibition promotes Hem-SCs proliferation, angiogenesis, and adipocyte differentiation by attenuating PI3K/AKT signaling.
Authors: Weidong Wang, Sheng Chen, Yuan Wang, Cui Jie, Weimin Shen
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,024
Funder: Nanjing Medical University
OpenAlex ID: W4413875765