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Induction of Circadian Gene Expression in Human Subcutaneous Adipose‐derived Stem Cells
Author(s) -
Wu Xiying,
Zvonic Sanjin,
Floyd Z. Elizabeth,
Kilroy Gail,
Goh Brian C.,
Hernandez Teri L.,
Eckel Robert H.,
Mynatt Randall L.,
Gimble Jeffrey M.
Publication year - 2007
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1038/oby.2007.308
Subject(s) - endocrinology , circadian rhythm , adipose tissue , adipocyte , medicine , biology , adipogenesis , stem cell , per1 , cellular differentiation , circadian clock , microbiology and biotechnology , clock , gene , biochemistry
Objective: Genes encoding the circadian transcriptional apparatus exhibit robust oscillatory expression in murine adipose tissues. This study tests the hypothesis that human subcutaneous adipose‐derived stem cells (ASCs) provide an in vitro model in which to monitor the activity of the core circadian transcriptional apparatus. Research Methods and Procedures: Primary cultures of undifferentiated or adipocyte‐differentiated ASCs were treated with dexamethasone, rosiglitazone, or 30% fetal bovine serum. The response of undifferentiated ASCs to dexamethasone was further evaluated in the presence of lithium chloride. Lithium inhibits glycogen synthase kinase 3, a key component of the circadian apparatus. Total RNA was harvested at 4‐hour intervals over 48 hours and examined by real‐time reverse transcription polymerase chain reaction (RT‐PCR). Results: Adipocyte‐differentiated cells responded more rapidly to treatments than their donor‐matched undifferentiated controls; however, the period of the circadian gene oscillation was longer in the adipocyte‐differentiated cells. Dexamethasone generated circadian gene expression patterns with mean periods of 25.4 and 26.7 hours in undifferentiated and adipocyte‐differentiated ASCs, respectively. Both rosiglitazone and serum shock generated a significantly longer period in adipocyte‐differentiated ASCs relative to undifferentiated ASCs. The Bmal1 profile was phase‐shifted by ∼8 to 12 hours relative to Per1, Per3 , and Cry2 , consistent with their expression in vivo. Lithium chloride inhibited adipogenesis and significantly lengthened the period of Per3 and Rev‐erb α gene expression profiles by >5 hours in dexamethasone‐activated undifferentiated ASCs. Discussion: These results support the initial hypothesis and validate ASCs as an in vitro model for the analysis of circadian biology in human adipose tissue.