Autocrine fibroblast growth factor 2 signaling is critical for self-renewal of human multipotent adipose-derived stem cells

Autor: Gérard Ailhaud, Christian Dani, Laure-Emmanuelle Zaragosi
Přispěvatelé: Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)
Jazyk: angličtina
Rok vydání: 2006
Předmět:
Male
MESH: Signal Transduction
Cellular differentiation
MAP Kinase Kinase 1
MESH: Receptors
Fibroblast Growth Factor
Cell morphology
Fibroblast growth factor
Regenerative medicine
0302 clinical medicine
Adipocytes
MESH: Protein Kinase Inhibitors
Phosphorylation
[SDV.BDD]Life Sciences [q-bio]/Development Biology
Mitogen-Activated Protein Kinase 1
0303 health sciences
Mitogen-Activated Protein Kinase 3
Cell Differentiation
MESH: Nitriles
3. Good health
Cell biology
Autocrine Communication
Adipose Tissue
Child
Preschool
030220 oncology & carcinogenesis
Molecular Medicine
Fibroblast Growth Factor 2
MESH: MAP Kinase Kinase 1
Stem cell
Signal transduction
MESH: Mitogen-Activated Protein Kinase 3
MESH: Adipose Tissue
Signal Transduction
Adult stem cell
MESH: Mitogen-Activated Protein Kinase 1
MESH: Cell Differentiation
Biology
Colony-Forming Units Assay
MESH: Butadienes
03 medical and health sciences
MESH: Cell Proliferation
Nitriles
Butadienes
Humans
MESH: Cell Shape
MESH: Colony-Forming Units Assay
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Autocrine signalling
Cell Shape
Protein Kinase Inhibitors
MESH: Adipocytes
Cell Proliferation
030304 developmental biology
MESH: Humans
MESH: Phosphorylation
MESH: Fibroblast Growth Factor 2
Multipotent Stem Cells
MESH: Child
Preschool
Cell Biology
Receptors
Fibroblast Growth Factor
MESH: Male
Pyrimidines
MESH: Pyrimidines
MESH: Multipotent Stem Cells
MESH: Autocrine Communication
Developmental Biology
Zdroj: Stem cells (Dayton, Ohio)
Stem cells (Dayton, Ohio), 2006, 24 (11), pp.2412-9. ⟨10.1634/stemcells.2006-0006⟩
DOI: 10.1634/stemcells.2006-0006⟩
Popis: Adipose tissue-derived stem cells offer tremendous potential for regenerative medicine. However, characterization of their self-renewal ability has not been performed yet, although it is a crucial feature for in vitro expansion of undifferentiated cells and in vivo maintenance of stem cell pools. We have undertaken the identification of molecular events that are involved in in vitro self-renewal of human multipotent adipose-derived stem (hMADS) cells from young donors, by assessing their proliferation rate, their ability to grow at the single-cell level (clonogenicity), and their differentiation potential. As hMADS cells are propagated in culture, cell morphology changes dramatically, concomitantly to a progressive decrease in proliferation, clonogenicity, and differentiation potential. This decrease is associated with a decrease in fibroblast growth factor 2 (FGF2) expression and can be circumvented by chronic treatment with exogenous FGF2. Moreover, analysis of FGF2 secretion revealed that it is exported to hMADS cell surface without being released into the culture medium, suggesting a strictly autocrine loop. Indeed, treatment of FGF2-expressing hMADS cells with PD173074, a specific FGF receptor inhibitor, decreases dramatically their clonogenicity and differentiation potential. Thus, hMADS cells express a functional autocrine FGF loop that allows maintenance of their self-renewal ability in vitro. Finally, inhibition of mitogen-activated protein kinase kinase 1 reduces the clonogenic potential of hMADS cells but does not affect their differentiation potential, indicating that the extracellular signal-related kinases 1/2 signaling pathway is partly involved in FGF2-mediated self-renewal. Together, our data clearly identify the key function of FGF2 in the maintenance of self-renewal of adipose tissue-derived stem cells.
Databáze: OpenAIRE
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