Functional differentiation of stem cell-derived neurons from different murine backgrounds

Abstract

Murine stem cell-derived neurons have been used to study a wide variety of neuropsychiatric diseases with a hereditary component, ranging from autism to Alzheimer’s. While a significant amount of data on their molecular biology has been generated, there is little data on the physiology of these cultures. Different mouse strains show clear differences in behavioral and other neurobiologically relevant readouts. We have studied the physiology of early differentiation and network formation in neuronal cultures derived from three different mouse embryonic stem cell lines. We have found largely overlapping patterns with some significant differences in the timing of the functional milestones. Neurons from R1 showed the fastest development of intrinsic excitability, while E14Tg2a and J1 were slower. This was also reflected in an earlier appearance of synaptic activity in R1 cultures, while E14Tg2a and J1 were delayed by up to 2 days. In conclusion, stem cells from all backgrounds could be successfully differentiated into functioning neural networks with similar developmental patterns. Differences in the timing of specific milestones, suggest that control cell lines and time-points should be carefully chosen when investigating genetic alterations that lead to subtle deficits in neuronal function.

PRMT1 and PRMT8 Regulate Retinoic Acid-Dependent Neuronal Differentiation with Implications to Neuropathology

“…1B; Supporting Information Fig. S1A), this is in line with the findings of others on ESC derived neurons differentiated using the same method .…”

Bcl-xL Promotes the Survival of Motor Neurons Derived from Neural Stem Cells

“…The entire procedure generated induced motor neurons in 5 days, and the resulting induced cells expressed specific marker HB9 and mature marker MAP2. This duration was faster than that in previous observations using wild−type NPCs, and those NSCs differentiated into specific neurons by small molecules [36]. Preclinical studies documented that wild−type NPCs need 2−3 weeks to form MAP + neurons [26,27].…”

Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering

“…Electrophysiological experiments allowed us to further investigate how neuron-like these cells were. Neurophysiological changes are expected as the NSCs differentiate, and are influenced by many factors. − To the best of our knowledge, no such data has been recorded from de novo-designed gels. Whole-cell patch-clamp recordings showed large voltage-gated K + currents; ion channels that play a key role in shaping neural activity in vivo, on hSAF gels.…”