Academic Journal

3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis

التفاصيل البيبلوغرافية
العنوان: 3D Adipose Tissue Culture Links the Organotypic Microenvironment to Improved Adipogenesis
المؤلفون: Joanne X. Shen, Morgane Couchet, Jérémy Dufau, Thais de Castro Barbosa, Maximilian H. Ulbrich, Martin Helmstädter, Aurino M. Kemas, Reza Zandi Shafagh, Marie‐Adeline Marques, Jacob B. Hansen, Niklas Mejhert, Dominique Langin, Mikael Rydén, Volker M. Lauschke
المصدر: Advanced Science, Vol 8, Iss 16, Pp n/a-n/a (2021)
بيانات النشر: Wiley, 2021.
سنة النشر: 2021
المجموعة: LCC:Science
مصطلحات موضوعية: adipose stem cells, fat cells, lipidomics, organotypic cell culture, preadipocytes, stromal vascular fraction, Science
الوصف: Abstract 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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2198-3844
Relation: https://doaj.org/toc/2198-3844
DOI: 10.1002/advs.202100106
URL الوصول: https://doaj.org/article/568a4d59aeaf495091d40d5a6daf16a5
رقم الانضمام: edsdoj.568a4d59aeaf495091d40d5a6daf16a5
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:21983844
DOI:10.1002/advs.202100106