RESUMEN
Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different developmental stages. Additionally, using multiplexed proteomic imaging and MALDI imaging mass spectrometry, we identify distinct histological and metabolic profiles for highly differentiated tumors. Our approaches are applicable to understanding the interplay between heterogeneity and differentiation in other cancers and can provide important insights for the design of targeted therapies.
Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Humanos , Proteínas Hedgehog/genética , Meduloblastoma/genética , Proteómica , Cerebelo , Neoplasias Cerebelosas/genéticaRESUMEN
Current developments being made in upper limb prostheses are focused on replacing lost sensory information to the amputees. Providing sensory stimulation from the prosthesis can directly improve control over the prosthetic and provide a sense of body ownership. The focus of this review article is on recent developments while including foundational knowledge for some of the critical concepts in neural prostheses. Reported concepts follow the flow of information from sensors to signal processing, with emphasis on texture recognition, and then to sensory stimulation strategies that reestablish the lost sensory feedback loop. Prosthetic sensors are used to detect the physical environment, converting pressure, force, and position into electrical signals. The electrical signals can then be processed in an effort to identify the surrounding environment using distinctive characteristics such as stiffness and texture. In order for the amputee to use this information in a natural manner, there must be real-time sensory stimulation, perception, and motor control of the prosthesis. Although truly complete sensory replacement has not yet been realized, some basic percepts can be partially restored, allowing progress towards a more realistic prosthesis with natural sensations.