Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells

Mechanical
interactions between cells and extracellular matrix
(ECM) are critical for stem cell fate decision. Synthetic models of
ECM, such as hydrogels, can be used to precisely manipulate the mechanical
properties of the cell niche and investigate how mechanical signals
regulate the cell behavior. However, it has long been a great challenge
to tune solely the ECM-mimic hydrogels’ mechanical signals
since altering the mechanical properties of most materials is usually
accompanied by chemical and topological changes. Here, we employ DNA
and its enantiomers to prepare a series of hydrogels with univariate
stiffness regulation, which enables a precise interpretation of the
fate decision of neural progenitor cells (NPCs) in a three-dimensional
environment. Using single-cell RNA sequencing techniques, Monocle
pseudotime trajectory and CellphoneDB analysis, we demonstrate that
the stiffness of the hydrogel alone does not influence the differentiation
of NPCs, but the degradation of the hydrogel that enhances cell–cell
interactions is possibly the main reason. We also find that ECM remodeling
facilitates cells to sense mechanical stimuli.