Prospective Approach to Deciphering the Impact of Intercellular Mitochondrial Transfer from Human Neural Stem Cells and Brain Tumor-Initiating Cells to Neighboring Astrocytes

The communication between neural stem cells (NSCs) and surrounding astrocytes is essential for the homeostasis of the NSC niche. Intercellular mitochondrial transfer, a unique communication system that utilizes the formation of tunneling nanotubes for targeted mitochondrial transfer be-tween donor and recipient cells, has recently been identified in a wide range of cell types. Intercel-lular mitochondrial transfer has also been observed between different types of cancer stem cells (CSCs) and their neighboring cells, including brain CSCs and astrocytes. CSC mitochondrial transfer significantly enhances overall tumor progression by reprogramming neighboring cells. Despite the urgent need to investigate this newly identified phenomenon, mitochondrial transfer in the central nervous system remains largely uncharacterized. In this study, we found evidence of intercellular mitochondrial transfer from human NSCs and from brain CSCs, also known as brain tumor-initiating cells (BTICs), to astrocytes in co-culture experiments. Both NSC and BTIC mito-chondria triggered similar transcriptome changes upon transplantation into the recipient astro-cytes. In contrast to NSCs, the transplanted mitochondria from BTICs had a significant prolifera-tive effect on the recipient astrocytes. This study forms the basis for mechanistically deciphering the impact of intercellular mitochondrial transfer on recipient astrocytes, which will potentially provide us with new insights into the mechanisms of mitochondrial retrograde signaling. Astrocytes were transplanted with mitochondria that was extracted from Radia Glia (RG) cells or Brain tumor initiating cells (BTIC), that were compared with the non-transplanted astrocytes as a control. The RNA was extracted from the cells after 7 days of cell culture with the transplanted mitochondria.