Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution

Anna Ehrlund; Niklas Mejhert; Christel Björk; Robin Andersson; Agné Kulyté; Gaby Åström; Masayoshi Itoh; Hideya Kawaji; Timo Lassmann; Carsten O. Daub; Piero Carninci; Alistair R. R. Forrest; Yoshihide Hayashizaki; Albin Gustav Sandelin; Erik Ingelsson; null FANTOM Consortium; Mikael Rydén; Jurga Laurencikiene; Peter Arner; Erik Arner

doi:10.2337/db16-0631

Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution

Anna Ehrlund, Niklas Mejhert, Christel Björk, Robin Andersson, Agné Kulyté, Gaby Åström, Masayoshi Itoh, Hideya Kawaji, Timo Lassmann, Carsten O. Daub, Piero Carninci, Alistair R. R. Forrest, Yoshihide Hayashizaki, Albin Gustav Sandelin, Erik Ingelsson, FANTOM Consortium, Mikael Rydén, Jurga Laurencikiene, Peter Arner, Erik Arner

Computational and RNA Biology

15 Citations (Scopus)

Abstract

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. Singlemolecule 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.

Original language	English
Journal	Diabetes
Volume	66
Issue number	1
Pages (from-to)	218-230
Number of pages	13
ISSN	0012-1797
DOIs	https://doi.org/10.2337/db16-0631
Publication status	Published - 1 Jan 2017

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Ehrlund, A., Mejhert, N., Björk, C., Andersson, R., Kulyté, A., Åström, G., Itoh, M., Kawaji, H., Lassmann, T., Daub, C. O., Carninci, P., Forrest, A. R. R., Hayashizaki, Y., Sandelin, A. G., Ingelsson, E., FANTOM Consortium, Rydén, M., Laurencikiene, J., Arner, P., & Arner, E. (2017). Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution. Diabetes, 66(1), 218-230. https://doi.org/10.2337/db16-0631

Ehrlund, A, Mejhert, N, Björk, C, Andersson, R, Kulyté, A, Åström, G, Itoh, M, Kawaji, H, Lassmann, T, Daub, CO, Carninci, P, Forrest, ARR, Hayashizaki, Y, Sandelin, AG, Ingelsson, E, FANTOM Consortium, Rydén, M, Laurencikiene, J, Arner, P & Arner, E 2017, 'Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution', Diabetes, vol. 66, no. 1, pp. 218-230. https://doi.org/10.2337/db16-0631

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title = "Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution",

abstract = "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. Singlemolecule 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.",

author = "Anna Ehrlund and Niklas Mejhert and Christel Bj{\"o}rk and Robin Andersson and Agn{\'e} Kulyt{\'e} and Gaby {\AA}str{\"o}m and Masayoshi Itoh and Hideya Kawaji and Timo Lassmann and Daub, {Carsten O.} and Piero Carninci and Forrest, {Alistair R. R.} and Yoshihide Hayashizaki and Sandelin, {Albin Gustav} and Erik Ingelsson and {FANTOM Consortium} and Mikael Ryd{\'e}n and Jurga Laurencikiene and Peter Arner and Erik Arner",

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T1 - Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution

AU - Ehrlund, Anna

AU - Mejhert, Niklas

AU - Björk, Christel

AU - Andersson, Robin

AU - Kulyté, Agné

AU - Åström, Gaby

AU - Itoh, Masayoshi

AU - Kawaji, Hideya

AU - Lassmann, Timo

AU - Daub, Carsten O.

AU - Carninci, Piero

AU - Forrest, Alistair R. R.

AU - Hayashizaki, Yoshihide

AU - Sandelin, Albin Gustav

AU - Ingelsson, Erik

AU - FANTOM Consortium, null

AU - Rydén, Mikael

AU - Laurencikiene, Jurga

AU - Arner, Peter

AU - Arner, Erik

PY - 2017/1/1

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N2 - 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. Singlemolecule 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.

AB - 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. Singlemolecule 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.

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DO - 10.2337/db16-0631

M3 - Journal article

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SN - 0012-1797

VL - 66

SP - 218

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JO - Diabetes

JF - Diabetes

IS - 1

ER -

Transcriptional dynamics during human adipogenesis and its link to adipose morphology and distribution

Abstract

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