Novel venom-based peptides (P13 and its derivative—M6) to maintain self-renewal of human embryonic stem cells by activating FGF and TGFβ signaling pathways

Abstract

Background: In our previous study, a venom-based peptide named Gonearrestide (also named P13) was identified and demonstrated with an effective inhibition in the proliferation of colon cancer cells. In this study, we explored if P13 and its potent mutant M6 could promote the proliferation of human embryonic stem cells and even maintain their self-renewal. Methods: The structure-function relationship analysis on P13 and its potent mutant M6 were explored from the molecular mechanism of corresponding receptor activation by a series of inhibitor assay plus molecular and dynamics simulation studies. Results: An interesting phenomenon is that P13 (and its potent mutant M6), an 18AA short peptide, can activate both FGF and TGFβ signaling pathways. We demonstrated that the underlying molecular mechanisms of P13 and M6 could cooperate with proteoglycans to complete the "dimerization" of FGFR and TGFβ receptors. Conclusions: Taken together, this study is the first research finding on a venom-based peptide that works on the FGF and TGF-β signaling pathways to maintain the self-renewal of hESCs.

Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs

“… 58 Ma et al reported that short peptides, P13 and M6, which support the self-renewal of hESCs, bound to the plasma membrane without penetrating into cytoplasm. 59 To examine whether WWASKS penetrates into the cytosol, we carried out a cell fractionation experiment. The FITC-peptide untreated group served as a control for the experiment.…”

Human embryonic stem cells cultured on hydrogels grafted with extracellular matrix protein‐derived peptides with polyethylene glycol joint nanosegments

“…Several researchers have developed ECM‐derived peptide‐immobilised dishes for the proliferation of hPSCs [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Melkoumian et al.…”

“…Several researchers have developed ECM‐derived peptide‐immobilised dishes for the proliferation of hPSCs [11–26]. Melkoumian et al.…”

“…Several researchers have developed ECM-derived peptideimmobilised dishes for the proliferation of hPSCs [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Melkoumian et al reported for the first time that ECM-derived peptide-grafted surfaces can support the expansion of hPSCs for over 12 passages [21].…”

Peptide Conjugate on Multilayer Graphene Oxide Film for the Osteogenic Differentiation of Human Wharton’s Jelly-Derived Mesenchymal Stem Cells

“…The utilization of synthetic peptides as a component within engineered biomaterials is now a standard technique [ 34 , 35 , 36 , 37 ]. Recently, researchers have focused on identifying and exploring the use of peptide and peptide derivatives as potential candidates for the development of 2D or 3D cell-culture materials to tailor the stem cell’s microenvironment to further improve the adhesion, proliferation, and differentiation of stem cells [ 38 , 39 , 40 , 41 ]. For instance, peptides have been grafted to a variety of synthetic polymers to endow the material with cell-adhesive, enzymatically degradable, and growth-factor-binding properties [ 42 , 43 ].…”