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Nat Cell Biol DOI:10.1038/ncb2411

Programming human pluripotent stem cells into white and brown adipocytes.

Publication TypeJournal Article
Year of Publication2012
AuthorsAhfeldt, T, Schinzel, RT, Lee, Y-K, Hendrickson, D, Kaplan, A, Lum, DH, Camahort, R, Xia, F, Shay, J, Rhee, EP, Clish, CB, Deo, RC, Shen, T, Lau, FH, Cowley, A, Mowrer, G, Al-Siddiqi, H, Nahrendorf, M, Musunuru, K, Gerszten, RE, Rinn, JL, Cowan, CA
JournalNat Cell Biol
Volume14
Issue2
Pages209-19
Date Published2012 Jan 15
ISSN1476-4679
Keywords3T3 Cells, Adipocytes, Brown, Adipocytes, White, Adipose Tissue, Brown, Adipose Tissue, White, Animals, CCAAT-Enhancer-Binding Protein-beta, Cell Differentiation, Cells, Cultured, Cluster Analysis, DNA-Binding Proteins, Gene Expression Profiling, HEK293 Cells, Humans, Immunohistochemistry, Mesenchymal Stem Cell Transplantation, Mesenchymal Stromal Cells, Mice, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Pluripotent Stem Cells, PPAR gamma, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transgenes, Transplantation, Heterologous
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.

URLhttp://dx.doi.org/10.1038/ncb2411
DOI10.1038/ncb2411
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/22246346?dopt=Abstract

Alternate JournalNat. Cell Biol.
PubMed ID22246346
PubMed Central IDPMC3385947
Grant ListP30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK095384 / DK / NIDDK NIH HHS / United States
U01 HL107440 / HL / NHLBI NIH HHS / United States