Role of glycosphingolipid SSEA‐3 and FGF2 in the stemness and lineage commitment of multilineage differentiating stress enduring (MUSE) cells. Issue 1 (12th October 2022)

• Record Type: Journal Article
• Authors: Aprile, Domenico; Alessio, Nicola; Squillaro, Tiziana; Di Bernardo, Giovanni; Peluso, Gianfranco; Galderisi, Umberto
• Is Part Of: Cell proliferation. Volume 56:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-12
• Subjects: Cell proliferation -- Periodicals; 571.84
• DOI: 10.1111/cpr.13345
• Languages: English
• ISSNs: 0960-7722

Abstract

Abstract: Objectives: Multilineage differentiating Stress Enduring (MUSE) cells are endogenous, stress‐resistant stem cells, expressing pluripotency master genes and able to differentiate in cells of the three embryonic sheets. Stage‐Specific Embryonic Antigen 3 (SSEA‐3), a glycosphingolipid (GSL), is the marker for identifying MUSE cells and is used to isolate this population from mesenchymal stromal cells. GSLs modulate signal transduction by interacting with plasma membrane components. The growth factor FGF2, important for MUSE cells biology, may interact with GSLs. Specific cell surface markers represent an invaluable tool for stem cell isolation. Nonetheless their role, if any, in stem cell biology is poorly investigated. Functions of stem cells, however, depend on niche external cues, which reach cells through surface markers. We addressed the role of SSEA‐3 in MUSE cell behaviour, trying to define whether SSEA‐3 is just a marker or if it plays a functional role in this cell population by determining if it has any relationship with FGF2 activity. Results: We evidenced how the SSEA‐3 and FGF2 cooperation affected the self‐renewal and clonogenic capacity of MUSE cells. The block of SSEA‐3 significantly reduced the multilineage potential of MUSE cells with production of nullipotent clones. Conclusions: We contributed to dissecting the mechanisms underlying MUSE cell properties for establishing successful stem‐cell‐based therapies and the promotion of MUSE cells as a tool for the in vitro disease model. Abstract : We demonstrated that SSEA‐3, a glycosphingolipid (GSL), may act as an FGF‐2 co‐receptor in MUSE cell, this activates the FGF2 signalling cascade mainly through PI3K mediation. Our study is one of the first evidence attributing GSL a functional role in governing stem cell biology. (A) Experimental plan. (B) Effect of cultivation of MUSE cells with SSEA3 inhibition. (C) SSEA‐3—FGF2 interaction and pathway.