The Role of ROR2 Expression in Predicting Differentiation of Human Induced Pluripotent Stem Cells into Neural Stem/Progenitor Cells and GABAergic Neurons
Human induced pluripotent stem cells (hiPSCs) hold great promise for regenerative medicine and disease modeling due to their ability to differentiate into various cell types. One area of particular interest is the differentiation of hiPSCs into neural stem/progenitor cells (NSPCs) and gamma-aminobutyric acid (GABA) producing neurons, known as GABAergic neurons. These neurons play a crucial role in the central nervous system, regulating inhibitory neurotransmission and maintaining the balance between excitation and inhibition.
However, the efficiency and reliability of differentiating hiPSCs into NSPCs and GABAergic neurons remain a challenge. Researchers are constantly exploring new markers and factors that can predict and enhance the differentiation process. One such marker is the receptor tyrosine kinase-like orphan receptor 2 (ROR2).
ROR2 is a transmembrane protein that belongs to the ROR family of receptor tyrosine kinases. It is involved in various developmental processes, including skeletal and neuronal development. Recent studies have shown that ROR2 expression is closely associated with the differentiation potential of hiPSCs into NSPCs and GABAergic neurons.
In a study published in Stem Cell Reports, researchers investigated the role of ROR2 expression in predicting the differentiation of hiPSCs into NSPCs and GABAergic neurons. They found that ROR2 expression was significantly upregulated during the early stages of neural induction. Moreover, they observed that high levels of ROR2 expression were correlated with a higher efficiency of NSPC differentiation.
Further experiments revealed that ROR2 expression was not only a predictor of NSPC differentiation but also played a functional role in promoting the generation of GABAergic neurons. Knockdown of ROR2 expression resulted in a significant reduction in the number of GABAergic neurons generated from hiPSCs. Conversely, overexpression of ROR2 led to an increase in GABAergic neuron production.
The researchers also investigated the underlying mechanisms by which ROR2 promotes NSPC differentiation and GABAergic neuron generation. They found that ROR2 activation stimulated the Wnt/β-catenin signaling pathway, which is known to play a crucial role in neural development. Activation of this pathway enhanced the expression of key transcription factors involved in NSPC differentiation and GABAergic neuron specification.
These findings highlight the importance of ROR2 expression as a potential biomarker for predicting the differentiation potential of hiPSCs into NSPCs and GABAergic neurons. By assessing ROR2 expression levels, researchers can identify hiPSC lines with a higher propensity for neural differentiation, thus improving the efficiency and reliability of generating NSPCs and GABAergic neurons.
Furthermore, understanding the molecular mechanisms by which ROR2 promotes NSPC differentiation and GABAergic neuron generation opens up new avenues for enhancing the differentiation process. Manipulating ROR2 expression or activating the Wnt/β-catenin signaling pathway could potentially be used to improve the yield and purity of NSPCs and GABAergic neurons, making them more suitable for therapeutic applications.
In conclusion, ROR2 expression plays a crucial role in predicting the differentiation potential of hiPSCs into NSPCs and GABAergic neurons. Its upregulation during neural induction is associated with a higher efficiency of NSPC differentiation, while its functional role in promoting GABAergic neuron generation highlights its importance as a biomarker. Further research into the underlying mechanisms and potential therapeutic applications of ROR2 in neural differentiation will undoubtedly contribute to the advancement of regenerative medicine and disease modeling.
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