Abstract
Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We delivered a 10% static equibiaxial stretch to NSPCs and examined effects on differentiation. We found static stretch specifically impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Generation of oligodendrocytes from NSPCs was reduced on laminin, an outcome likely mediated by the α6 laminin-binding integrin, whereas similar effects were not observed for NSPCs on fibronectin. Our data demonstrate a direct role for tensile strain in dictating the lineage choice of NSPCs and indicate the dependence of this phenomenon on specific substrate materials, which should be taken into account for the design of biomaterials for NSPC transplantation.
Highlights
Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice
We found no direct effect of static stretch on the differentiation of mouse NSPCs (mNSPCs) into neurons or astrocytes, which will be discussed further in a later section
A single static stretch applied at the onset of differentiation and maintained for several days induced a 2.6-fold reduction in O4-positive oligodendrocytes and a 3.2-fold reduction in earlier stage oligodendrocytes detected by PDGFR-a (Figs. 3a and S1)
Summary
Neural stem and progenitor cell (NSPC) fate is strongly influenced by mechanotransduction as modulation of substrate stiffness affects lineage choice. Other types of mechanical stimuli, such as stretch (tensile strain), occur during CNS development and trauma, but their consequences for NSPC differentiation have not been reported. We found static stretch impacts NSPC differentiation into oligodendrocytes, but not neurons or astrocytes, and this effect is dependent on particular extracellular matrix (ECM)-integrin linkages. Stem cells are the only cells in the body capable of indefinite self-renewal and differentiation into various cell types In vivo, they reside within specific microenvironments, or niches, that contain various chemical and physical signals affecting cell function. Uniaxial cyclic strain increases the expression of smooth muscle markers from hMSCs8–10 This active mechanical stimulus coordinates with TGF-b, a soluble factor that induces smooth muscle markers in these cells, to affect MSC differentiation[10]. Since mechanical forces are at play during development and in cases of trauma, it is important to determine their effects on NSPC differentiation
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