Abstract
The utility of human pluripotent stem cells is dependent on efficient differentiation protocols that convert these cells into relevant adult cell types. Here we report the robust and efficient differentiation of human pluripotent stem cells into white or brown adipocytes. We found that inducible expression of PPARG2 alone or combined with CEBPB and/or PRDM16 in mesenchymal progenitor cells derived from pluripotent stem cells programmed their development towards a white or brown adipocyte cell fate with efficiencies of 85%-90%. These adipocytes retained their identity independent of transgene expression, could be maintained in culture for several weeks, expressed mature markers and had mature functional properties such as lipid catabolism and insulin-responsiveness. When transplanted into mice, the programmed cells gave rise to ectopic fat pads with the morphological and functional characteristics of white or brown adipose tissue. These results indicate that the cells could be used to faithfully model human disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Adipocytes, Brown / cytology
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Adipocytes, Brown / metabolism*
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Adipocytes, White / cytology
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Adipocytes, White / metabolism*
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Adipose Tissue, Brown / cytology
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Adipose Tissue, Brown / metabolism
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Adipose Tissue, White / cytology
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Adipose Tissue, White / metabolism
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Animals
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CCAAT-Enhancer-Binding Protein-beta / genetics
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CCAAT-Enhancer-Binding Protein-beta / metabolism
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Cell Differentiation / genetics*
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Cells, Cultured
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Cluster Analysis
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Gene Expression Profiling
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HEK293 Cells
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Humans
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Immunohistochemistry
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Mesenchymal Stem Cell Transplantation / methods
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Mesenchymal Stem Cells / cytology
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Mesenchymal Stem Cells / metabolism
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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PPAR gamma / genetics
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PPAR gamma / metabolism
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Pluripotent Stem Cells / cytology
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Pluripotent Stem Cells / metabolism*
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transgenes / genetics*
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Transplantation, Heterologous
Substances
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CCAAT-Enhancer-Binding Protein-beta
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CEBPB protein, human
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DNA-Binding Proteins
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PPAR gamma
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PRDM16 protein, human
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Transcription Factors