TD2-Gene-3D – Epigenetic analysis of physiological 3D adipose tissue models

This cooperative project, with the University of Hohenheim, is funded by the Baden-Württemberg Stiftung.

The main goals within the project are

  • The development of a physiological hydrogelmatrix for culture and differentiation of adipose-derived stem cells (ASCs)
  • The establishment of an extrusionbased bioprinting process for reproducible production of tissue models
  • The setup physiological tissue models with genetic variants to validate lean and obese cells noncoding risk loci  

The translation of epigenic findings of cells – cultured in a physiological three-dimensional (3D) matrix – to adipose tissue associated diseases is striven. Genome-wide association studies have identified hundreds of genetic loci associated with Type 2 Diabetes (T2D). However, translating these findings into therapeutics has remained a great challenge.

One bottleneck is that the genetic etiology of T2D primarily stems from the non-coding part of the genome, reflected in changes in the epigenome. Non-coding variants impact T2D risk by altering proximal and distal gene regulatory elements, making it difficult to dissect their mechanism of action. The dissection of genetic risk loci is further confounded by the lack of appropriate cell models mimicking microenvironment and three dimensionality of tissue situation.

Such physiological 3D models are used to resemble the in vivo situation as close as possible, regarding important features like proteins or stiffness. Culturing cells in a physiological 3D environment is more clinically relevant as standardly used tissue culture plastic, to study gene regulation as culture conditions directly affect the epigenetic state.

Aim of this project is the mechanistic decoding of non-coding risk loci of T2D using bioprinted physiological 3D adipose tissue models.

Project duration: 03/2019 until 02/2022

Contact:Franziska Albrecht, Petra Kluger