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. 2024 Nov 26;14:29286. doi: 10.1038/s41598-024-76984-9

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© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — Isolation and analysis of “twin” cells present in SKOV3 cultures. Panel A: “twin” cells as shown in Fig. 3 (Panel A, A-D and Panel B, A-C) were subjected to mechanical isolation using a one-arm micromanipulator. At least 20 “twin” cells and a proportional amount of surrounding normal cells were collected for single-cell RNA isolation. Panel B: qPCR transcriptional analysis of “twin” cells vs. normal epithelia-shaped cells. A dual neuronal-stem signature is detected at the transcriptional level. Some markers were not detected (red triangles): NeuroN, SOX2 in normal cells and CD24 and EpCAM in “twin” cells. Panel C: I: Cartoon representing OC cells acquiring a neuron-like morphology under the influence of platinum-derived compounds as seen in Fig. 1. A large cell (A) gradually condenses its cytoplasm and starts forming dendritic tree-like structures (B & C). The cytoplasm is finally dismantled until fully formed dendrite-like structures are left (C & D). These morphological changes correlate with the expression of a plethora of neuronal-defining markers. II: Diagrammatic representation of the modulation of pathways involved in EMT and from this point to a “neuro-mesenchymal” inter-condition or EMET based on the transcriptional and protein expression profiles. SKOV3 cells have a basal expression of several neuronal markers, which is enhanced by exposure to sub-toxic concentrations of platinum-derived drugs. The expression of cardinal stemness markers like Nanog, Notch1, SOX2, and Klf-4 suggests the acquisition of cancer stem cells status. The cells that have moved to a neuroepithelial condition are in a transitory status of dormancy. Results are representative of n = 3 experiments.

Fig. 6 — Isolation and analysis of “twin” cells present in SKOV3 cultures. Panel A: “twin” cells as shown in Fig. 3 (Panel A, A-D and Panel B, A-C) were subjected to mechanical isolation using a one-arm micromanipulator. At least 20 “twin” cells and a proportional amount of surrounding normal cells were collected for single-cell RNA isolation. Panel B: qPCR transcriptional analysis of “twin” cells vs. normal epithelia-shaped cells. A dual neuronal-stem signature is detected at the transcriptional level. Some markers were not detected (red triangles): NeuroN, SOX2 in normal cells and CD24 and EpCAM in “twin” cells. Panel C: I: Cartoon representing OC cells acquiring a neuron-like morphology under the influence of platinum-derived compounds as seen in Fig. 1. A large cell (A) gradually condenses its cytoplasm and starts forming dendritic tree-like structures (B & C). The cytoplasm is finally dismantled until fully formed dendrite-like structures are left (C & D). These morphological changes correlate with the expression of a plethora of neuronal-defining markers. II: Diagrammatic representation of the modulation of pathways involved in EMT and from this point to a “neuro-mesenchymal” inter-condition or EMET based on the transcriptional and protein expression profiles. SKOV3 cells have a basal expression of several neuronal markers, which is enhanced by exposure to sub-toxic concentrations of platinum-derived drugs. The expression of cardinal stemness markers like Nanog, Notch1, SOX2, and Klf-4 suggests the acquisition of cancer stem cells status. The cells that have moved to a neuroepithelial condition are in a transitory status of dormancy. Results are representative of n = 3 experiments.