Abstract
BackgroundDistinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers.Methodology/Principal FindingsWe used dielectrophoresis (DEP) to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates.Conclusions/SignificanceWe show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors.
Highlights
Stem cells self-renew and generate progenitors capable of further differentiation into specialized cell types
The identities of cells differentiated from human neural stem/progenitor cell (huNSPC) were confirmed by determining the presence of neuron and astrocyte markers by immunostaining and assessing cell morphological criteria
SC27 huNSPCs had a lower propensity to generate astrocytes (Fig. 1b) and GFAPpositive/sox2-positive cells (Fig. S1b) than SC23 cells, but had higher levels of cells that were only sox2-positive than SC23 cells (Fig. S1b)
Summary
Stem cells self-renew and generate progenitors capable of further differentiation into specialized cell types. Developmental neurobiology studies of the rodent cortex identified resident stem cells that predominantly generate neurons at early stages of brain formation and glia at later stages, suggesting the presence of neuron-biased (or potentially neuron-restricted) progenitors at early stages and progenitors linked to glial fates at later times [1,2,3,4,5,6]. Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers
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