Malignant Glioma is characterized by strong self-renewal potential and immature differentiation potential. The main reason is that malignant glioma holds key cluster cells, glioma stem cells (GSCs). GSCs contribute to tumorigenesis, tumor progression, recurrence, and treatment resistance. Interferon-beta (IFN-β) is well known for its anti-proliferative efficacy in diverse cancers. IFN-β also displayed potent antitumor effects in malignant glioma. IFN-β affect both GSCs and Neural stem cells (NSCs) in the treatment of gliomas. However, the functional comparison, similar or different effects of IFN-β on GSCs and NSCs are rarely reported. Here, we studied the similarities and differences of the responses to IFN-β between human GSCs and normal NSCs. We found that IFN-β preferentially inhibited GSCs over NSCs. The cell body and nucleus size of GSCs increased after IFN-β treatment, and the genomic analysis revealed the enrichment of the upregulated immune response, cell adhesion genes and down regulated cell cycle, ribosome pathways. Several typical cyclin genes, including cyclin A2 (CCNA2), cyclin B1 (CCNB1), cyclin B2 (CCNB2), and cyclin D1 (CCND1), were significantly downregulated in GSCs after IFN-β stimulation. We also found that continuous IFN-β stimulation after passage further enhanced the inhibitory effect. Our study revealed how genetic diversity resulted in differential effects in response to IFN-β treatment. These results may contribute to improve the applications of IFN-β in anti-cancer immunotherapy. In addition, these results may also help to design more effective pharmacological strategies to target cancer stem cells while protecting normal neural stem cells.

Stem cell-based therapies have been used for repairing damaged brain tissue and helping functional recovery after brain injury. Aberrance neurogenesis is related with brain injury, and multipotential neural stem cells from human embryonic stem (hES) cells provide a great promise for cell replacement therapies. Optimized protocols for neural differentiation are necessary to produce functional human neural stem cells (hNSCs) for cell therapy. However, the qualified procedure is scarce and detailed features of hNSCs originated from hES cells are still unclear. In this study, we developed a method to obtain hNSCs from hES cells, by which we could harvest abundant hNSCs in a relatively short time. Then, we examined the expression of pluripotent and multipotent marker genes through immunostaining and confirmed differentiation potential of the differentiated hNSCs. Furthermore, we analyzed the mitotic activity of these hNSCs. In this report, we provided comprehensive features of hNSCs and delivered the knowledge about how to obtain more high-quality hNSCs from hES cells which may help to accelerate the NSC-based therapies in brain injury treatment.

Ovarian cancer (OC), particularly high-grade serous cancer (HGSC), is the leading cause of mortality among gynecological cancers owing to the treatment difficulty and high recurrence probability. As therapeutic drugs approved for OC, poly ADP-ribose polymerase inhibitors (PARPi) lead to synthetic lethality by inhibiting single-strand DNA repair, particularly in homologous recombination-deficient cancers. However, even PARPi have distinct efficacies and are prone to have drug resistance, the molecular mechanisms underlying the PARPi resistance in OC remain unclear. A patient-derived organoid platform was generated and treated with a PARPi to understand the factors associated with PARPi resistance. PARPi significantly inhibits organoid growth. After 72 h of treatment, both the size of organoids and the numbers of adherent cells decreased. Moreover, immunofluorescence results showed that the proportion of Ki67 positive cells significantly reduced. When the PARPi concentration reached 200 nM, the percentage of Ki67⁺/4′,6-diamidino-2-phenylindole (DAPI) cells decreased approximately 50%. PARPi treatment also affected the expression of genes involved in base excision repair and cell cycle. Functional assays revealed that PARPi inhibits cell growth by upregulating early apoptosis. The expression levels of several key genes were validated. In addition to previously reported genes, some promising genes FEN1 and POLA2, were also be founded. The results demonstrate the complex effects of PARPi treatment on changes in potential genes relevant to PARPi resistance, and provide perspectives for further research on the PARPi resistance mechanisms.

The mammalian central nervous system (CNS) has a limited ability to renew the damaged cells after a brain or spinal cord injury whether it is nonhuman primates like monkeys or humans. Transplantation of neural stem cells (NSCs) is a potential therapy for CNS injuries due to their pluripotency and differentiation abilities. Cytokines play an important role in CNS development and repair of CNS injuries. However, the detailed cytokine signaling response in monkey neural stem cells is rarely studied. In our previous research, we isolated NSCs from the adult monkey brain and found the effects of cytokines on monkey NSCs. Now, we further analyzed the regulation mechanisms of cytokines to the proliferation of monkey NSCs such as bone morphogenic protein 4 (BMP4), BMP4/leukaemia inhibitory factor (LIF), or retinoic acid (RA)/Forskolin. The data showed that BMP4 inhibited cell proliferation to arrest, but it did not affect the stemness of NSCs. BMP4/LIF promoted the astrocyte‐like differentiation of monkey NSCs, and RA/forskolin induced the neuronal differentiation of monkey NSCs. BMP4/LIF and RA/forskolin induced monkey NSC differentiation by regulating Notch signaling. These results provide some theoretical evidence for NSC therapy to brain or spinal cord injury in regenerative medicine.