ECTS - University of Pisa
Dato che la lingua ufficiale del corso è l'inglese, potete consultare tutte le informazioni presenti sulla versione in inglese.
We are entering into a new era in which a fundamental understanding of developmental biology and regeneration will play a critical role. In this course, embryonic and adult stem cells in different organisms will be examined in terms of their molecular, cellular, and potential therapeutic properties. Somatic reprogramming, directed differentiation, and somatic conversion methodologies will be critically evaluated.
During the examination the student will be assessed on his/her knowledge and deep critical understanding of the topics dealt with during the course with a focus on the student's ability to link different topics in a comprehensive view.
The student will be able to critically evaluate the stem cell contribution in unique developmental processes and to recapitulate the required instructions/stimuli to propagate stem cell populations in vitro or direct them towards specific fates under defined conditions. Somatic reprogramming will be critically discussed.
Oral exam, with discussion of the topics analyzed during the class and critical discussions of the original articles provided.
Critical ability to evaluate stem cell contribution in developmental processes, disease modeling or therapeutic approaches.
Acquired skills will be tested during discussion on lecture, presentation of relevant papers by the students, and final exam.
Knowledge of cell, molecular, or developmental biology is recommended.
Frontal lessons and paper discussion.
STEM CELLS
Main features of stem cells. Self-renewal and differentiation. Asymmetric and symmetric cell divisions. Transit amplifying cells. Totipotency, pluripotency and multipotency. Generalities and applications of stem cells. Molecular mechanics driving cell differentiation at the morula stage. Cell fate decision leading to trophectoderm, primitive endoderm and epiblast: the role of transcription factors.
Embryonic Stem Cells (ESCs)
Origin of ESCs. The ESC ability to self-renew and to produce differentiated cells is controlled by dynamic interplays between epigenetic, extrinsic signaling, transcriptional and post-transcriptional regulations. Molecular details of pluripotency: OCT4, SOX2, NANOG. LIF signaling pathway. A KLF core regulates self-renewal of ESCs. Cooperative lineage restriction by BMP4/Id and LIF/STAT3. ESCs and regulation of the cell cycle. Differentiation of ESCs.
Induced Pluripotent Stem Cells (iPSCs)
Introduction to induced pluripotency. Yamanaka discovery: first generation of iPSCs (2006). The second generation of iPSCs. iPSCs without c-Myc. New methods for iPSC generation: Thomson contribution (2007). Improving the speed and efficiency of iPSC generation. Reprogramming with Vitamin C. Transgene-free iPSCs. Genetic reprogramming vs. chemical reprogramming. Disease modeling. Development of pluripotent stem cell-based therapies.
Adult Stem Cells
Role of stem cells in adult tissues. Concept of niche. Mesenchymal and hematopoietic stem cells. Epidermal stem cells, limbal stem cells of the corneal epithelium. Intestinal stem cells. Neural stem cells. Identification and function of quiescent and activated stem cells in selected tissues. Role of extrinsic and intrinsic factors in adult stem cells. Generation of organoids. Therapeutic approaches.
NEURAL STEM CELLS (NSCs)
Introduction to NSCs and neurogenesis. How to build a brain. Historical perspective.
Early neurogenesis in mammalian development: initial regional specification of NSCs; different types of NSCs. Neuroepithelial cells and radial glial cells. Early neurogenic phase and symmetric versus asymmetric divisions.
Late neurogenesis in mammalian development: middle and late neurogenic phases, gliogenesis. Outer radial glia in human cortical development and evolution.
Adult SVZ neurogenic niche: structure and definition of the NSC component. Physiological relevance of adult SVZ neurogenesis: olfactory neurons, relevance in human. Adult hippocampal SGZ neurogenic niche: structure and definition of the NSC component, rodent versus human. Physiological relevance of adult hippocampal neurogenesis.
NSCs in vitro: tissue-derived systems, neurospheres and adherent cell culture.
NSCs and neurogenesis in vitro: pluripotent stem cell-derived neural systems. Neural induction and directed neural differentiation.
NSCs in disease: neurodevelopmental and neurodegenerative disorders.
Regenerative approaches to the CNS: cell transplantation in Parkinson’s disease, Huntington’s disease, and spinal cord injury.
Advanced 3D neural systems: retina and brain organoids. Direct reprogramming of neural fate.
No textbook is required for the course. Given that much of the material in this class will be contemporary, there is no comprehensive textbook that adequately covers all topics. As a result, the main reference material will be the Lecture slides themselves. Lecture slides will be available on e-learning together with select reviews and original articles.
For a good general resource covering early development and neurodevelopment, the following Text books are suggested:
All the information and didactic material will be provided on the website of the course.
Oral exam in English or Italian, up to the student.
Unimap: https://unimap.unipi.it/cercapersone/dettaglio.php?ri=120679&template=dett_didattica.tpl
Esami: https://esami.unipi.it/esami/findcourse.php?id=38171
