GSE106504
Neuronal differentiation of DFATs
Transplantation of functional neurons improve the functionally recovery in animal models of Alzheimer's disease and other neurological disorders. Although functional neurons can be differentiated from embryonic stem cells or induced-pluripotent stem cells, alternative cell sources of functional neurons may be more available for transplantation. Dedifferentiated fat cells (DFATs) were isolated and cultured from mature adipose tissue, which have advantages in their abundance, ease of isolation and homogeneity compared to other adult stem cells. DFATs are promising for clinical applications such as cell transplation therapy.    Direct reprogramming has been developed in recent years. It is possible to convert mature differentiated cells into other types of functional cells by introducing cell-fate-conversion transcriptional factors. However, the introduction of exogenous transcriptional factors limits their use of clinical application. Previous studies found that in vitro neuronal differentiation follows the processes of in vivo neuronal development, which are related to the surrounding microenvironments. Therefore, the arrangement of a proper microenvironment for the neuronal development process is essential to induce neuronal differentiation.      In this study, we report that DFATs differentiated into neurons by all trans retinoic acid (ATRA) and basic fibroblast growth factor (bFGF). The ATRA/bFGF-treated DFATs expressed the neuron-specific mRNA and pritein expression, exibited neuron-like morphology, generated voltage-dependent sodium current and action potentials and react with neurotransmitters. Transcriptomics resutls suggested that ATRA/bFGF treatment induced a specific differentiatioin into neurons. The lesional analysis revealed that ATRA/bFGF-treated cells are compatible with telemcephalon gabaergic neuron. To investigate the mechanism of ATRA/bFGF-induced neuronal differentiation, we performed the pathway analysis. The pathway analysis suggested that JNK signaling pathway was involved in the neuronal diffeerentiation. Our knockdown experiient further demonstrated that JNK3, a neuronal subtype of JNK, plays a crucial role in ATRA/bFGF-induced neuronal differentiation.    In conclusion, we demonstrated that ATRA/bFGF induced DFATs into functional neurons via the activation of JNK3 signaling pathway. Our study provides an efficient approach for generating functional neurons from adult fat tissue and reveals the functional importance of JNK3 in neuronal differentiation process. Overall design: Total of 6 samples were analyze. 3 biological replicate for control or ATRA+bFGF treatment.