CdSBIOLOGIA MOLECOLARE E CELLULARE
Codice518EE
CFU6
PeriodoPrimo semestre
LinguaInglese
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, somatic conversion, and organoid generation will be critically evaluated.
The students’ knowledge will be through the active participation in frontal lessons and by direct interaction between teacher and students during class activities to favor comments and in-depth analysis of the topics presented. For real-time verification of the effectiveness of learning and to arouse interest in the discipline, the teacher presents questions about the topics of the lessons.
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.
It will be possible to assess the acquisition of the skills during interactive frontal lessons and planned journal clubs which should provide tangible elements and direct experience in stem cells.
The student will be driven to evaluate the efficiency and complexity of methodologists and experimental approaches. He/she will develop the critical ability to evaluate stem cell contribution in developmental processes, disease modeling or therapeutic approaches.
The degree of attainment of the behaviours will be observed during the course, including through classroom interventions and, particularly, during journal clubs.
Students are invited to verify the existence of any prerequisites by consulting the Regulations of the Study Program relating to their year of enrolment.An exam taken in violation of the propaedeutic rules is void (University teaching regulations, art. 24, paragraph 3).
Knowledge of cell, molecular, or developmental biology is recommended.
The module will take the form of frontal lessons supported by seminars. Here students will be able to present and discuss reports and original papers. The course will be held in English.
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:
- Scott F. Gilbert and Michael J. Barresi. Developmental Biology (XI Edition)
- Dan H. Sanes, Thomas A. Reh, William A. Harris. Development of the Nervous System (III Edition)
There are no specific indications for nonattending students; the examination procedures and the program remain unchanged. We remind you thatoffice hours are there for the student to ask clarification of complex topics, the most effective methods for the study of the subject, or for any other insights.
All the information and didactic material are provided on the website of the course.
The exam is oral. The student must answer correctly to the questions proposed by the examination board, demonstrating an adequate ability to make connections among the key themes addressed in the module. Exam would be in English or Italian, up to the student.
Unimap:
https://unimap.unipi.it/cercapersone/dettaglio.php?ri=4937&template=dett_didattica.tpl
https://unimap.unipi.it/cercapersone/dettaglio.php?ri=120679&template=dett_didattica.tpl
Exams: https://esami.unipi.it/esami/findcourse.php?id=38171
Examination Committee:
President: Prof. Massimiliano Andreazzoli
Members: Prof. Marco Onorati, Dr. Matteo Digregorio
Substitute members: Prof. Michela Ori, Dr. Claudia Dell'Amico, Dr. Alessia Muscò