NEUROG2( Neurogenin 2)

Functional characterization of the grafted hES-iNs and their impact on the balance between brain excitation and inhibition is now highly warranted. This new stem cell source should be considered when, in the future, the most suitable candidate will be selected for clinical translation.

Following doxycycline-induction of Ngn2, we observed more rapid and efficient differentiation, and improved neurite outgrowth and viability compared with the WT cell line. Moreover, when co-cultured with C2C12 mouse myotubes, the modified NG108-15 cells resulted in significantly larger acetylcholine receptor (AChR) aggregates, suggesting enhanced neuromuscular junction (NMJ) formation. These findings describe a novel methodology for differentiating NG108-15 cells more efficiently, to enhance the usefulness of the cell line as a motor neuron model.

Furthermore, our observations indicate that Neurog2-driven modulation of PTFs potentially contribute to NEPC development. Thus, targeting Neurog2 holds promise as an effective therapeutic strategy for MYCN-overexpressing NEPC.

These results underscore the pivotal role of SOXC factors' transcriptional repression and illuminate one of their specific downstream targets.

Lineage re-specification of rat cortical OPCs occurred without prior injury, demonstrating these glial progenitor cells need not be put into a reactive state to achieve lineage reprogramming. These results show it may be feasible to precisely engineer additional neurons directly in adult cerebral cortex for experimental study or potentially for therapeutic use to modify dysfunctional or damaged circuitry.

Stringent fate mapping techniques independently of an AAV-based expression system are the golden standard for tracing the fate of glia cells during neuronal reprogramming. The newly developed AAV-based systems are invaluable tools for glia-to-neuron reprogramming in vivo.

This demonstrated upregulation of the neuronal commitment markers upon hypoxia exposure, while no change was observed in astrocytic and oligodendrocyte lineage commitment markers. Increased expression of downstream targets of the WNT signaling pathway, TCF4 and ID2, by qPCR (n = 9) and increased protein expression of CTNNB1 (β-catenin) and ID2 by Western blot (n = 3) indicated its involvement in mediating neuronal differentiation upon exposure to hypoxia.

Interestingly, ectopic PAX3 expression in PAX3b-depleted SK-N-SH cells enhanced neuronal outgrowth along with neuronal marker gene induction. Collectively, these results showed that the PAX3b isoform may be responsible for the differentiation defect observed in SK-N-SH cells and restoration of functional PAX3 in the absence of PAX3b can induce neurogenesis in these cells.

The Hes genes exhibit oscillatory expression levels, and this dynamic expression allows for the complex regulation of numerous downstream genes such as Ascl1, Neurog2, Olig2 involved in the differentiation of specific cell types. In addition, HES proteins act as hubs for the molecule crosstalk among Notch, Wnt, and other signaling pathways that regulate nervous system development.

This suggests that Chd4 is expressed across various cell types throughout development and that partial loss of Chd4 may impact cortex size and anxiety behaviours in male germline heterozygotes. This may help elucidate the genetic basis of specific Chd4 variants, including those noted in SIHIWES.

These results suggest that GBM cells can be reprogrammed into different subtypes of neurons, leading to a potential alternative approach to treat brain tumors using in vivo cell conversion technology.

Starting with nine clusters at embryonic day 14.5, we clarified the differentiation of lineage of all clusters in later stages. Our results indicate that the spatial differentiation of embryonic PC clusters is involved in forming the basic cerebellar organization of the mouse brain.