Articles
Vol. 69 No. 3 (2025)
Effects of Notch signaling on proliferation, angiogenesis, and adipogenesis of hemangioma-derived stem cells
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 1 September 2025
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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.
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Ethics Approval
the protocol of this study was approved by the Ethics Committee of Children's Hospital of Nanjing Medical UniversitySupporting Agencies
The current study was supported by the Science and Technique Development Foundation of Nanjing Medical University (NMUB2020088).How to Cite
1.
Wang W, Chen S, Wang Y, Jie C, Shen W. Effects of Notch signaling on proliferation, angiogenesis, and adipogenesis of hemangioma-derived stem cells. Eur J Histochem [Internet]. 2025 Sep. 1 [cited 2025 Dec. 26];69(3). Available from: https://www.ejh.it/ejh/article/view/4241
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