Stem Cells 2

07 May 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 1. The molecular logic of necortical neuron specification, development and diversity. Investigating the evolution of pallial development: an example fro the literature. 2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size.

13 May 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 2. HLH proneural genes regulate different binaries choice in mammalian corticogenesis: examples from the literature. Selection of differentiating cells by different levels of delta-like 1 among neural precursor cells in the developing mouse telencephalon. The role of Notch in primate cortical expansion: Human-Specific NOTCH2NL genes expand cortical neurogenesis through delta/notch regulation.

20 May 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 3. An overview of human cerebral organoids. Brain organoids to model neurodevelopmental diseases. Main differences of corticogenesis between the mouse model, primates and humans. The contribute of the pionier "brainmaker" Yoshiki Sasai. The school of Jurgen Knoblich: the first reported cerberal organoid in 2014. The capability of human cerebral organoids to reproduce key aspects of the human corticogenesis, such as the formation of outer radial glia progeniotr cells.

27 May 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 4. Establishing Cerebral Organoids as Models of Human-Specific Brain Evolution. The main difference between tissue and organoids is the ratio of supragranular neuron layers. Analysis of mTOR pathway genes reveals that both activators (INSR, ITGB8, IFNAR1) and repressors (PTEN) are strongly upregulated in human organoids and human primary cells. Primate cell fusion disentangles gene regulatory divergence in neurodevelopment. The analysis of human-primate hybrid organoids reveals a signature of selection on astrocyte-related genes. In addition, the human somatostatin receptor 2 gene (SSTR2), which regulates neuronal calcium signalling and is associated with neuropsychiatric disorders, is also upregulated. The use o cerebral organoids is a promising tool to address molecular mechanisms of brain primate evolution.

03 Jun 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 5. Investigating normal and pathological human cortical neurons. The Sliced Neocortical Organoid (SNO) Method. SNO resolves interior hypoxia and reduces cell death. Many human SNO cells exhibit the hallmark unipolar morphology of oRGs and express human oRG markers. SNO develop supragranular layer neurons. SNO model the DISC1 disease associated with schizophrenia, major depression, and autism. SparCon assays of iPSC-derived SHANK2 ASD neurons allows Investigating developmental defects related to SHANK2 cognitive disorder in adhernt cultures.

10 Jun 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 6. Modelling the development a neural network with the complete repertoire of human cortical neurons for functional studies: assembly of functionally integrated human forebrain spheroids. Forebrain spheroids can be assembled in vitro to recapitulate the saltatory migration of interneurons observed in the fetal forebrain. Modeling of the Timothy syndrome and preliminary assay of drugs to restore interneuron migration.

21 Jun 2024 (2h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 7. Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Induction and neurogenic conversion of ES-cell-derived midbrain ventral precursors is dependent on CHIR addition. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia.

08 Oct 2024 (6h 00m)

Federico Cremisi - Course (teaching activity) - Face to face

Lesson 8, 9, 10. Lesson 8: The developmental trajectory of electrophysiological properties in Cerebral Organoids: studies correlating them with morphological and cellular features. Potential of COs as a valuable tool for neuroscience research. Lesson 9: Transplanted human cortical organoids integrate into host brain circuits, demonstrating their potential for modeling human development and disease. By studying these transplanted organoids, researchers can uncover circuit-level phenotypes in patient-derived cells that would be difficult to observe in vitro. Lesson 10: iPSC-derived cerebral organoids (COs) provide a valuable model for studying Alzheimer's disease (AD). Recent studies demonstrated that COs derived from patients with familial AD forms developed AD-specific markers and exhibited tissue patterning defects and altered development, suggesting premature neuronal differentiation.