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3D Adipose Tissue C...
3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis
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- Shen, J. X. (author)
- Karolinska Institutet
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Couchet, M. (author)
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Dufau, J. (author)
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- de Castro Barbosa, T. (author)
- Karolinska Institutet
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Ulbrich, M. H. (author)
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Helmstädter, M. (author)
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- Kemas, A. M. (author)
- Karolinska Institutet
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- Shafagh, Reza Zandi (author)
- Karolinska Institutet,KTH,Mikro- och nanosystemteknik,Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 171 77 Sweden
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Marques, M. -A (author)
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Hansen, J. B. (author)
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- Mejhert, N. (author)
- Karolinska Institutet
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Langin, D. (author)
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- Rydén, M. (author)
- Karolinska Institutet
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- Lauschke, V. M. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2021-06-24
- 2021
- English.
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In: Advanced Science. - : Wiley. - 2198-3844. ; 8:16
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Abstract
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- Obesity and type 2 diabetes are strongly associated with adipose tissue dysfunction and impaired adipogenesis. Understanding the molecular underpinnings that control adipogenesis is thus of fundamental importance for the development of novel therapeutics against metabolic disorders. However, translational approaches are hampered as current models do not accurately recapitulate adipogenesis. Here, a scaffold-free versatile 3D adipocyte culture platform with chemically defined conditions is presented in which primary human preadipocytes accurately recapitulate adipogenesis. Following differentiation, multi-omics profiling and functional tests demonstrate that 3D adipocyte cultures feature mature molecular and cellular phenotypes similar to freshly isolated mature adipocytes. Spheroids exhibit physiologically relevant gene expression signatures with 4704 differentially expressed genes compared to conventional 2D cultures (false discovery rate < 0.05), including the concerted expression of factors shaping the adipogenic niche. Furthermore, lipid profiles of >1000 lipid species closely resemble patterns of the corresponding isogenic mature adipocytes in vivo (R2 = 0.97). Integration of multi-omics signatures with analyses of the activity profiles of 503 transcription factors using global promoter motif inference reveals a complex signaling network, involving YAP, Hedgehog, and TGFβ signaling, that links the organotypic microenvironment in 3D culture to the activation and reinforcement of PPARγ and CEBP activity resulting in improved adipogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- adipose stem cells
- fat cells
- lipidomics
- organotypic cell culture
- preadipocytes
- stromal vascular fraction
- transcriptomics
- Molecular weight
- Signaling
- Tissue
- Tissue culture
- 3D adipose tissue
- Cellular phenotypes
- Differentially expressed gene
- False discovery rate
- Gene expression signatures
- Metabolic disorders
- Microenvironments
- Signaling networks
- Transcription
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Shen, J. X.
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Couchet, M.
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Dufau, J.
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de Castro Barbos ...
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Ulbrich, M. H.
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Helmstädter, M.
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show more...
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Kemas, A. M.
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Shafagh, Reza Za ...
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Marques, M. -A
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Hansen, J. B.
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Mejhert, N.
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Langin, D.
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Rydén, M.
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Lauschke, V. M.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Advanced Science
- By the university
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Royal Institute of Technology
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Karolinska Institutet