Adipocytes derived from PA6 cells reliably promote the differentiation of dopaminergic neurons from human embryonic stem cells.
The PA6 stromal cell line comprises a heterogeneous population of cells that can induce both mouse and human embryonic stem cells to differentiate into dopaminergic neurons. This ability of PA6 cells has been termed stromal cell-derived inducing activity (SDIA). The level of SDIA has been found to vary considerably between and within batches of PA6 cells. Not only are the molecular mechanisms that underlie SDIA unknown but also the cell type(s) within the heterogeneous PA6 cultures that underlie SDIA remain poorly defined. In this study, we reveal that adipocytes, which are present within the heterogeneous PA6 cell population, robustly release the factors mediating SDIA. Furthermore, we report that the coculture of human embryonic stem cells with PA6-derived adipocytes reliably induces their differentiation into midbrain dopaminergic neurons.
Neuronal Survival Unit, Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund, Sweden.
M O
MO
Guloglu
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A
Larsen
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P
Brundin
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D054377:Chemokine CXCL12 / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D059290:Dopaminergic Neurons / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000187:drug effects / Q000502:physiology*; D036387:Ephrin-B1 / Q000378:metabolism; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C515255:CXCL12 protein, human; D002352:Carrier Proteins; D054377:Chemokine CXCL12; D016207:Cytokines; C484288:EFNB1 protein, human; D036387:Ephrin-B1; C035170:IGF2 protein, human; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; C066845:pleiotrophin; D007335:Insulin-Like Growth Factor II; D014446:Tyrosine 3-Monooxygenase; D015056:1-Methyl-3-isobutylxanthine; D004298:Dopamine
PA6; Parkinson's disease; adipocyte; dopaminergic differentiation; hESC