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Institute for Bioengineering and Biosciences
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Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids

Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Cerebellar Organoids | iBB | Scoop.it

 

Endogenous human brain tissue is not easily available for studying neurodevelopment and neurodegenerative diseases. However, human pluripotent stem cells (PSCs) have been used to generate a variety of glial and neuronal cells of the central nervous system. Still, reproducible protocols for generating in vitro models of the human cerebellum are scarce. In this context, Silva et al. describe the scalable production of human PSC-derived cerebellar organoids using single-use vertical-wheel bioreactors. The transcriptomic profile of cerebellar organoids derived under dynamic conditions demonstrates a faster cerebellar differentiation combined with significant enrichment of extracellular matrix and upregulation of transcripts involved in angiogenesis when compared with the static protocol. The authors anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

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Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-Culture

Maturation of Human Pluripotent Stem Cell-Derived Cerebellar Neurons in the Absence of Co-Culture | iBB | Scoop.it

In a new paper published in Frontiers in Bioengineering and Biotechnology, SCERG-iBB researchers in collaboration with colleagues from the Institute of Molecular Medicine (iMM) describe a novel differentiation strategy that uses defined medium to generate Purkinje cells, granule cells, interneurons, and deep cerebellar nuclei projection neurons, that self-formed and matured into electrically active cells. This research is expected to result in better models for the study of cerebellar dysfunctions and represent an important advancement towards the development of autologous replacement strategies for treating cerebellar degenerative diseases.

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Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids

Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids | iBB | Scoop.it

Engineering brain organoids from human induced pluripotent stem cells (hiPSCs) is a powerful tool for modeling brain development and neurological disorders. Rett syndrome (RTT), a rare neurodevelopmental disorder, can greatly benefit from this technology, since it affects multiple neuronal subtypes in forebrain sub-regions. SCERG-iBB researchers have recently established dorsal and ventral forebrain organoids from control and RTT patient-specific hiPSCs recapitulating the 3D organization and functional network complexity of this brain region. The data obtained revealed a premature development of the deep-cortical layer, associated to the formation of TBR1 and CTIP2 neurons, and a lower expression of neural progenitor/proliferative cells in RTT dorsal organoids. Moreover, calcium imaging and electrophysiology analysis demonstrated functional defects of RTT neurons. Additionally, assembly of RTT dorsal and ventral organoids revealed impairments of interneuron’s migration. Overall, these models provide a better understanding of RTT during early stages of neural development, demonstrating a great potential for personalized diagnosis and drug screening. The paper was published in Frontiers in Cell Development Biology.

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