GDF5 induces TBX3 in a concentration dependent manner - on a gold nanoparticle gradient

L Andreasson; H Evenbratt; S Simonsson

doi:10.1016/j.heliyon.2020.e04133

GDF5 induces TBX3 in a concentration dependent manner - on a gold nanoparticle gradient

Heliyon. 2020 Jun 10;6(6):e04133. doi: 10.1016/j.heliyon.2020.e04133. eCollection 2020 Jun.

Authors

L Andreasson^{1

2}, H Evenbratt¹, S Simonsson²

Affiliations

¹ Cline Scientific AB, Mölndal, SE-431 53, Sweden.
² Institute of Biomedicine at Sahlgrenska Academy, Department of Clinical Chemistry and Transfusion Medicine, University of Gothenburg, Gothenburg, SE-413 45, Sweden.

Abstract

Organs and tissues, such as cartilage and limbs, are formed during development through an orchestration of growth factors that function as morphogens. Examples of growth factors include growth differentiation factor 5 (GDF5) and transforming growth factors beta 1 and 3 (TGFβ-1 and TGFβ-3) which can specify creation of more than one cell type after forming a concentration gradient in vivo. Here, we studied the impact of morphogen gradients during differentiation of induced pluripotent stem cells (iPSCs) into the chondrocyte lineage. Cell budding zones, consisting of condensed cell aggregates, were observed only in gradients of GDF5. T-box transcription factor 3 (TBX3) was detected specifically in the budding zones (ranging from 500-1,500 particles/μm²) of nuclei and cell vesicles. A homogenous density of GDF5 of 900 particles/μm² on a surface induced budding and expression of TBX3 after five days in iPSCs. Therefore, we conclude that a gradient of GDF5, as well as the specific homogenous density of GDF5, support the induction of TBX3 in iPCSs. Moreover, differentiation of iPSCs first on GDF5 gradient or homogenous surfaces for five days and then in a three-dimensional structure for five weeks resulted in pellets that expressed TBX3.

Keywords: Biomolecules; Cell biology; Cell culture; Cell differentiation; Chondrocyte differentiation; Developmental biology; GDF5; Limb budding zone; Ln521; Molecular biology; Nano gradient; Regenerative medicine; SOX9; Spectroscopy; Stem cells research; TBX3; TGFb1; TGFb3; iPSC.