Transcriptional Dynamics During Human Adipogenesis and Its Link to Adipose Morphology and Distribution.
White adipose tissue (WAT) can develop into several phenotypes with different pathophysiological impact on type 2 diabetes. To better understand the adipogenic process, the transcriptional events that occur during in vitro differentiation of human adipocytes were investigated and the findings linked to WAT phenotypes. Single-molecule transcriptional profiling provided a detailed map of the expressional changes of genes, enhancers, and long noncoding RNAs, where different types of transcripts share common dynamics during differentiation. Common signatures include early downregulated, transient, and late induced transcripts, all of which are linked to distinct developmental processes during adipogenesis. Enhancers expressed during adipogenesis overlap significantly with genetic variants associated with WAT distribution. Transiently expressed and late induced genes are associated with hypertrophic WAT (few but large fat cells), a phenotype closely linked to insulin resistance and type 2 diabetes. Transcription factors that are expressed early or transiently affect differentiation and adipocyte function and are controlled by several well-known upstream regulators such as glucocorticosteroids, insulin, cAMP, and thyroid hormones. Taken together, our results suggest a complex but highly coordinated regulation of adipogenesis.
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Anna
A
Ehrlund
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Niklas
N
Mejhert
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Christel
C
Björk
The Bioinformatics Centre, Department of Biology, and Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Robin
R
Andersson
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Agné
A
Kulyté
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Gaby
G
Åström
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Preventive Medicine & Diagnosis Innovation Program, Wakō, Saitama, Japan.
Masayoshi
M
Itoh
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Preventive Medicine & Diagnosis Innovation Program, Wakō, Saitama, Japan.
Hideya
H
Kawaji
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.|Telethon Kids Institute and The University of Western Australia, Perth, Western Australia, Australia.
Timo
T
Lassmann
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|Department of Biosciences and Nutrition and Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.
Carsten O
CO
Daub
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.
Piero
P
Carninci
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.
Alistair R R
AR
Forrest
RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Preventive Medicine & Diagnosis Innovation Program, Wakō, Saitama, Japan.
Yoshihide
Y
Hayashizaki
The Bioinformatics Centre, Department of Biology, and Biotech Research & Innovation Centre, University of Copenhagen, Copenhagen, Denmark.
Albin
A
Sandelin
Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.|Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
Erik
E
Ingelsson
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Mikael
M
Rydén
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Jurga
J
Laurencikiene
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden erik.arner@riken.jp peter.arner@ki.se.
Peter
P
Arner
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden erik.arner@riken.jp peter.arner@ki.se.|Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Tsurumi, Yokohama, Kanagawa, Japan.|RIKEN Omics Science Center, Tsurumi, Yokohama, Kanagawa, Japan.
Erik
E
Arner
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D050154:Adiposity / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D008066:Lipolysis / Q000235:genetics / Q000502:physiology; D025341:Principal Component Analysis; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
D034741:RNA, Small Interfering; D014157:Transcription Factors